Materiały źródłowe

• #1 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://www.mdpi.com/2072-6694/16/22/3858

  Liposarcomas (LSs) are rare mesenchymal soft-tissue sarcomas that are thought to arise from cells in the lipocyte lineages in soft tissues. […] The World Health Organization classifies over 100 soft-tissue sarcoma subtypes, which are characterized by distinct histologic and molecular profiles and variable clinical behavior. It classifies LSs into four subtypes based on histologic findings: well-differentiated LS (WDLS)/atypical lipomatous tumors (ALT), dedifferentiated LS (DDLS), myxoid LS (MLS), and pleomorphic LS (PLS). […] The presence of supernumerary abnormal chromosomes (extrachromosomal rings and/or giant rods) containing amplification from the 12q13-15 region are hallmark genetic alterations of both WDLS/ALT and DDLS. Frequently amplified genes include MDM2, CDK4, and HMGA2 and can be detected using IHC, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH).

• #2 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11592651/

  Liposarcomas (LSs) are rare mesenchymal soft-tissue sarcomas that are thought to arise from cells in the lipocyte lineages in soft tissues. […] The presence of supernumerary abnormal chromosomes (extrachromosomal rings and/or giant rods) containing amplification from the 12q13-15 region are hallmark genetic alterations of both WDLS/ALT and DDLS. […] DDLS cases often have high-level amplifications of chromosome 12 (12q14-15), which includes the CDK4 and MDM2 genes along with CPM, HMGA2 (coamplified with MDM2) and SAS/TSPAN31. […] MDM2 amplification is a nonspecific feature present in up to 40% of sarcomas; however, MDM2 is considered to be the main driver gene within the 12q amplicon, and its consistent amplification and overexpression may represent the earliest events in the development of LS.

• #3 Soft Tissues: Liposarcoma: Myxoid liposarcoma

  https://atlasgeneticsoncology.org/solid-tumor/5169/soft-tissues-liposarcoma-myxoid-liposarcoma

  Liposarcoma is the most common soft tissue malignancy in adults accounting for at least 20% of all sarcomas in this age group. […] Myxoid-round cell liposarcoma is a subtype of liposarcoma characterized by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11). This translocation creates the FUS-DDIT3 chimeric gene. […] Cytogenetics analyses have shown that several lipogenic tumours are characterized by specific chromosomal abnormalities, the best known was the reciprocal translocation t(12;16)(q13;p11) of myxoid-round cell liposarcoma, described about twenty years ago. This translocation results in a fusion gene consisting of the 5 part of the FUS (TLS) gene and the complete coding region of the CHOP gene. […] The involvement of a nuclear riboprotein in these processes in vivo indicates that FUS is important in genome maintenance.

• #4 Liposarcoma pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Liposarcoma_pathophysiology

  Liposarcoma is the most common sarcoma of soft tissue. The pathogenesis of liposarcoma depends on the histological sub-type. The two sub-types, well differentiated and dedifferentiated, are the two most commonly occurring liposarcomas. The majority of well differentiated liposarcomas arise in the retroperitoneum. The chromosome region 12q13-15, is rich in protooncogenes, including the CHOP, CDK4, MDM2, HMGI-C, GLI, SAS, OS1, and the OS9, all of which play an important role in the pathogenesis of many neoplasms. […] Liposarcoma is associated with genetic conditions like Li-Fraumeni syndrome. […] The dedifferentiated sub-type arises as a primary or de novo lesion in majority of the cases. The dedifferentiated sub-type is clinically more aggressive than the well differentiated liposarcoma.

• #5 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://www.mdpi.com/2072-6694/16/22/3858

  Liposarcomas (LSs) are rare mesenchymal soft-tissue sarcomas that are thought to arise from cells in the lipocyte lineages in soft tissues. […] The World Health Organization classifies over 100 soft-tissue sarcoma subtypes, which are characterized by distinct histologic and molecular profiles and variable clinical behavior. It classifies LSs into four subtypes based on histologic findings: well-differentiated LS (WDLS)/atypical lipomatous tumors (ALT), dedifferentiated LS (DDLS), myxoid LS (MLS), and pleomorphic LS (PLS). […] The presence of supernumerary abnormal chromosomes (extrachromosomal rings and/or giant rods) containing amplification from the 12q13-15 region are hallmark genetic alterations of both WDLS/ALT and DDLS. Frequently amplified genes include MDM2, CDK4, and HMGA2 and can be detected using IHC, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH).

• #6 Liposarcoma – Wikipedia

  https://en.wikipedia.org/wiki/Liposarcoma

  Liposarcomas arise from the precursor lipoblasts of the adipocytes (i.e. fat cells) in adipose (i.e. fat) tissues. […] The World Health Organization in 2020 reclassified liposarcomas into five more or less distinct forms: 1) atypical lipomatous tumor/well-differentiated liposarcoma (WD-LPS); 2) dedifferentiated liposarcoma (DD-LPS); 3) myxoid liposarcoma; 4) pleomorphic liposarcoma; and 5) myxoid pleomorphic liposarcoma. […] Studies to date find that all five liposarcoma forms, while usually treatable at least initially by surgical resection, are often only marginally responsive to currently used chemotherapy and radiotherapy regimens. […] The neoplastic cells in ALT/WDL tumors contain one or more extra ring-shaped small supernumerary marker chromosome (sSMC) or an abnormal giant marker chromosome (i.e. a formerly normal chromosome that is made abnormal by having a duplication of parts of its own or one or more other chromosome’s genetic material).

• #7 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  Liposarcoma is a complex tumor, and its pathophysiology can be best explained by dividing it into three subtypes (according to the World Health Organization (WHO) classification from 2002). These include well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS), myxoid and round cell liposarcoma (MLS and RCL), and pleomorphic liposarcoma (PLS). WDLPS/DDLPS will have a diagnostic giant marker and ring chromosome, which affects uncontrolled cell proliferation. For MCL and RCL, reciprocal translocation occurs between chromosomes 12 and 16, leading to the fusion of genes DDIT3 and FUS and subsequently activating some downstream targets such as PPARgamma2 and C/EBPalpha, promoting cell cycle proliferation. Pleomorphic liposarcoma is the most complex and least-understood of these. Mutations in various tumor suppressor pathways like p53, NF1, RB1 lead to many gains and account for the aggressive nature of this tumor.

• #8 Liposarcomas of the mediastinum – Suster – Mediastinum

  https://med.amegroups.org/article/view/5725/html

  Liposarcoma is a malignant tumor of adipocytic differentiation that rarely arises within the mediastinum. […] The World Health Organization (WHO) recognizes four basic types of liposarcoma: well-differentiated/atypical lipomatous tumor (ALT), dedifferentiated, myxoid and pleomorphic liposarcoma (PLS). […] Molecularly the most common subtypes of liposarcoma are characterized by specific, recurrent genetic alterations involving amplification events of MDM2 and CDK4 in well-differentiated liposarcoma (WDL) and a recurrent t(12;16)(q13;p11) in myxoid liposarcoma (MLS). […] In recent years, our understanding of these tumors has exponentially increased as molecular techniques have permitted better delineation of their oncogenic mechanisms. The molecular landscape of liposarcoma is defined primarily by two basic mechanisms of tumorigenesis. Well-differentiated/ALT and dedifferentiated liposarcomas (DDLS) are characterized by supernumerary ring and marker chromosomes that contain amplified sequences of chromosome region 12q13-15, including genes such as MDM2, CDK4 and CPM.

• #9 Novel Systemic Therapies in Advanced Liposarcoma: A Review of Recent Clinical Trial Results

  https://www.mdpi.com/2072-6694/5/2/529

  Liposarcoma is one of the most common adult soft tissue sarcomas and consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). […] Each subtype is characterized by distinct genetic and molecular aberrations and unique histologic appearance, suggesting separate pathways to malignant transformation. […] Well-differentiated (WD) and dedifferentiated (DD) liposarcoma are the most common subtype of liposarcoma. […] Both WD and DD tumor cells exhibit amplification of chromosome 12q13-15, a region which contains several hundred genes including MDM2, an inhibitor of the tumor suppressor p53, and CDK4, a critical regulator of cell cycling. […] Myxoid/round cell (MRC) liposarcoma is characterized by translocation of chromosomes 12 and 16 (t12;16)(q13;p11), that results in a fusion gene arrangement between FUS and CHOP/DDIT3.

• #10 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  Liposarcoma is a complex tumor, and its pathophysiology can be best explained by dividing it into three subtypes (according to the World Health Organization (WHO) classification from 2002). These include well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS), myxoid and round cell liposarcoma (MLS and RCL), and pleomorphic liposarcoma (PLS). WDLPS/DDLPS will have a diagnostic giant marker and ring chromosome, which affects uncontrolled cell proliferation. For MCL and RCL, reciprocal translocation occurs between chromosomes 12 and 16, leading to the fusion of genes DDIT3 and FUS and subsequently activating some downstream targets such as PPARgamma2 and C/EBPalpha, promoting cell cycle proliferation. Pleomorphic liposarcoma is the most complex and least-understood of these. Mutations in various tumor suppressor pathways like p53, NF1, RB1 lead to many gains and account for the aggressive nature of this tumor.

• #11 Frontiers | Targeting liposarcoma: unveiling molecular pathways and therapeutic opportunities

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1484027/full

  In recent years, an increasing number of studies have utilized molecular biology techniques to reveal important molecular heterogeneity among different subtypes of liposarcoma. Each subtype exhibits distinct genetic patterns and molecular pathways, which may serve as important targets for molecular therapy. […] In the present review, we discuss the molecular characteristics, molecular diagnostics, driver genes, and molecular pathogenesis of LPS. We also explore the corresponding therapeutic targets and downstream pathways, and summarize progress toward targeted therapies for several subtypes of LPS. […] The generation of different LPS subtypes is caused by their relatively unique driver genes and molecular mechanisms, which ultimately lead to large differences between subtypes. […] Progress in research into driver genes and molecular pathways has elucidated the mechanisms of LPS in a stepwise manner. These studies have also provided insights and guidance regarding the content and direction of clinical research.

• #12 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://www.mdpi.com/2072-6694/16/22/3858

  Liposarcomas (LSs) are rare mesenchymal soft-tissue sarcomas that are thought to arise from cells in the lipocyte lineages in soft tissues. […] The World Health Organization classifies over 100 soft-tissue sarcoma subtypes, which are characterized by distinct histologic and molecular profiles and variable clinical behavior. It classifies LSs into four subtypes based on histologic findings: well-differentiated LS (WDLS)/atypical lipomatous tumors (ALT), dedifferentiated LS (DDLS), myxoid LS (MLS), and pleomorphic LS (PLS). […] The presence of supernumerary abnormal chromosomes (extrachromosomal rings and/or giant rods) containing amplification from the 12q13-15 region are hallmark genetic alterations of both WDLS/ALT and DDLS. Frequently amplified genes include MDM2, CDK4, and HMGA2 and can be detected using IHC, chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH).

• #13 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11592651/

  Liposarcomas (LSs) are rare mesenchymal soft-tissue sarcomas that are thought to arise from cells in the lipocyte lineages in soft tissues. […] The presence of supernumerary abnormal chromosomes (extrachromosomal rings and/or giant rods) containing amplification from the 12q13-15 region are hallmark genetic alterations of both WDLS/ALT and DDLS. […] DDLS cases often have high-level amplifications of chromosome 12 (12q14-15), which includes the CDK4 and MDM2 genes along with CPM, HMGA2 (coamplified with MDM2) and SAS/TSPAN31. […] MDM2 amplification is a nonspecific feature present in up to 40% of sarcomas; however, MDM2 is considered to be the main driver gene within the 12q amplicon, and its consistent amplification and overexpression may represent the earliest events in the development of LS.

• #14 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  Liposarcoma is a malignant tumor of mesenchymal origin with significant tissue diversity. […] The histological classification of liposarcoma has become increasingly clear. […] More and more new methods and technologies, such as gene expression profile analysis, the whole genome sequencing, miRNA expression profile analysis and RNA sequencing, have been successfully applied to liposarcoma, bringing about a deeper understanding of gene expression changes and molecular pathogenic mechanisms in the occurrence and development of liposarcoma. […] Cytogenetic studies have showed that WDL/DDL is characterized by supernumerary ring chromosome and/or giant marker chromosome composed of amplified products from the q13-15 region on Chromosome No. 12. […] Many genes, such as MDM2, CDK4, HMGA2, CPM, SAS/TSPAN31, DYRK2, YEATS4 and others, amplify along with WDL/DDL.

• #15 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11592651/

  Liposarcomas (LSs) are rare mesenchymal soft-tissue sarcomas that are thought to arise from cells in the lipocyte lineages in soft tissues. […] The presence of supernumerary abnormal chromosomes (extrachromosomal rings and/or giant rods) containing amplification from the 12q13-15 region are hallmark genetic alterations of both WDLS/ALT and DDLS. […] DDLS cases often have high-level amplifications of chromosome 12 (12q14-15), which includes the CDK4 and MDM2 genes along with CPM, HMGA2 (coamplified with MDM2) and SAS/TSPAN31. […] MDM2 amplification is a nonspecific feature present in up to 40% of sarcomas; however, MDM2 is considered to be the main driver gene within the 12q amplicon, and its consistent amplification and overexpression may represent the earliest events in the development of LS.

• #16 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  Liposarcoma is a malignant tumor of mesenchymal origin with significant tissue diversity. […] The histological classification of liposarcoma has become increasingly clear. […] More and more new methods and technologies, such as gene expression profile analysis, the whole genome sequencing, miRNA expression profile analysis and RNA sequencing, have been successfully applied to liposarcoma, bringing about a deeper understanding of gene expression changes and molecular pathogenic mechanisms in the occurrence and development of liposarcoma. […] Cytogenetic studies have showed that WDL/DDL is characterized by supernumerary ring chromosome and/or giant marker chromosome composed of amplified products from the q13-15 region on Chromosome No. 12. […] Many genes, such as MDM2, CDK4, HMGA2, CPM, SAS/TSPAN31, DYRK2, YEATS4 and others, amplify along with WDL/DDL.

• #17 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://www.mdpi.com/2072-6694/16/22/3858

  DDLS has additional heterogeneous genetic changes compared with WDLS; in addition to the abnormalities in 12q14-15, there are more amplifications, particularly coamplifications of 6q23 and 1p32. […] MDM2 amplification is a nonspecific feature present in up to 40% of sarcomas; however, MDM2 is considered to be the main driver gene within the 12q amplicon, and its consistent amplification and overexpression may represent the earliest events in the development of LS.

• #18

  https://journals.lww.com/indianjcancer/fulltext/2013/50030/immunohistochemical_detection_of_p53_and_mdm2.2.aspx

  Liposarcomas develop through immature fat tissue cells called lipoblasts or more often from primitive mesenchymal cells. […] The MDM2 gene is localized in the 12q 13-14 chromosome. MDM2 amplification was observed in 30% of the sarcomas. MDM2 binds to the amino-terminal transcription region of p53 and inhibits transcription. MDM2 also induces the destruction of p53. […] Knowing the oncogenes that play a role in the pathogenesis of tumors is important in determining the treatment methods to be applied for such tumors. Mutation of the p53 gene accountable for tumor suppression results in the gene to become unable to suppress the tumor and also leads to the growth and spread of the tumor. […] The higher rate of p53 and MDM2 positivity compared to those with localization in the extremity in retroperitoneal liposarcoma suggests that p53 inhibition associated to MDM2 plays a role in the retroperitoneal liposarcoma pathogenesis in particular. […] The relationship between p53 and MDM2 expression and liposarcoma pathogenesis is unknown.

• #19 Atypical Lipomatous Tumor – SFA

  https://curesarcoma.org/sarcoma-subtypes/well-differentiated-liposarcoma-atypical-lipomatous-tumor/

  ALT is characterized by supernumerary ring and giant marker chromosomes, typically as the sole change or concomitant with a few other numerical or structural abnormalities. […] Both supernumerary rings and giant markers invariably contain amplified sequences originating from the 12q14-q15 region. MDM2 (12q15) being the main driver gene. […] Overexpression of MDM2 protein resulting from genomic amplification inactivates p53; MDM2 targets p53 degradation towards the proteasome and inhibits p53-mediated transactivation.

• #20 Liposarcoma: A Journey into a Rare Tumor’s Epidemiology, Diagnosis, Pathophysiology, and Limitations of Current Therapies

  https://www.mdpi.com/2072-6694/16/22/3858

  DDLS has additional heterogeneous genetic changes compared with WDLS; in addition to the abnormalities in 12q14-15, there are more amplifications, particularly coamplifications of 6q23 and 1p32. […] MDM2 amplification is a nonspecific feature present in up to 40% of sarcomas; however, MDM2 is considered to be the main driver gene within the 12q amplicon, and its consistent amplification and overexpression may represent the earliest events in the development of LS.

• #21 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  Both genes are proto-oncogenes, and the encoded proteins are involved in the regulation of cell cycles. […] MDM2 expression products are also transcriptional activation inhibitors of p53, which inhibit the transcription of p53 and lead to cell proliferation. […] However, for WDL/DDL, MDM2 amplification is accompanied by HMGA2 dysregulation, presenting its oncogenic property. […] The amplification of JUN or ASK1/MAP3K5 is related to the fact that WDL dedifferentiation leads to the tissue type changing to DDL. […] The systematic connection of the amplification of both genes and DDL occurrence has not been fully confirmed. […] The expression of anti-aging protein Klotho down-regulates in DDL compared with WDL and adipose tissue, which is related to poor prognosis; in addition, it can regulate the drug sensitivity of thapsigargin and gemcitabine by inhibiting ERK1/2 signal transduction, which provides a new therapeutic strategy for DDL.

• #22 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  Both genes are proto-oncogenes, and the encoded proteins are involved in the regulation of cell cycles. […] MDM2 expression products are also transcriptional activation inhibitors of p53, which inhibit the transcription of p53 and lead to cell proliferation. […] However, for WDL/DDL, MDM2 amplification is accompanied by HMGA2 dysregulation, presenting its oncogenic property. […] The amplification of JUN or ASK1/MAP3K5 is related to the fact that WDL dedifferentiation leads to the tissue type changing to DDL. […] The systematic connection of the amplification of both genes and DDL occurrence has not been fully confirmed. […] The expression of anti-aging protein Klotho down-regulates in DDL compared with WDL and adipose tissue, which is related to poor prognosis; in addition, it can regulate the drug sensitivity of thapsigargin and gemcitabine by inhibiting ERK1/2 signal transduction, which provides a new therapeutic strategy for DDL.

• #23 Alterations of the RB1 gene in dedifferentiated liposarcoma | Modern Pathology

  https://www.nature.com/articles/3800447

  The retinoblastoma gene (RB1) at chromosome 13q14 was originally identified as the gene responsible for the development of retinoblastoma and has served as a prototype of human tumor suppressor genes. […] Biallelic inactivation of RB1 is a hallmark not only of retinoblastoma, but has also been described in a variety of other tumors, including osteosarcoma and malignant fibrous histiocytoma. […] Schneider-Stock et al analyzed RB1-loss of heterozygosity (LOH) in 11 dedifferentiated liposarcoma patients and concluded that RB1-LOH plays an important role in the tumor progression of well-differentiated liposarcoma to dedifferentiated liposarcoma; however, whether or not there are alterations to the other allele in this tumor has not been previously ascertained. […] In the present study, we first performed LOH analysis using five microsatellite markers at 13q12q14 in 27 cases of dedifferentiated liposarcoma. […] The results suggest that pRB plays a role in dedifferentiation, and that two-hit mechanism is involved in the altered pRB expression in dedifferentiated liposarcoma.

• #24 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  The most prominent cytogenetic feature of MRCL is that about 95% of cases have specific t(12;16)(q13;p11) chromosomal translocation, which produces FUS-DDIT3 fusion protein, while about 5% of cases have t(12;22) (q13;q12) chromosomal translocation, producing EWSR1-DDIT3 fusion protein. […] These fusion proteins are important molecules for development of sarcoma and inhibition of adipogenesis and play crucial roles in the pathogenesis of MRCL. […] The expression level of FUS-DDIT3 fusion protein is also positively correlated with cell differentiation. […] Studies have shown that the FUS-DDIT3 fusion gene can enhance the invasion ability of MRCL by activating the SRC/FAK/RHO/ROCK signal axis, and the expression level of FAK is related to the degree of malignancy and the tumor grade. […] It has been shown that MRCL can cause gene mutation of EGFR, PDGFRB, RET, MET and VEGFR1 through the interaction of the autocrine/paracrine loop and the receptor tyrosine kinase (RTK), and it can keep activating the signaling pathway of the downstream PI3K/Akt, leading to the over-expression of growth factor receptor RET and IGF1R, which is related to the transformation of MLS to RCL, increasing invasiveness, and poor prognosis.

• #25 Liposarcomas of the mediastinum – Suster – Mediastinum

  https://med.amegroups.org/article/view/5725/html

  Myxoid liposarcoma (MLS), on the other hand, follows a different oncogenic mechanism and is characterized by a t(12;16)(q13;p11), which leads to the formation of a fusion oncogene: FUS-DDIT3 (DDIT3 was formerly known as CHOP) in 95% of cases or an EWSR1-DDIT3 in about 5% of cases. […] The role of immunohistochemistry and molecular pathology has been amply studied in these tumors. […] Like WDL, the diagnosis of DDLS is facilitated using antibodies for MDM2, which will show scattered nuclear positivity in the spindle cells of the non-lipogenic component as well as in the neoplastic adipocytic component. […] The histology of DDLS within the mediastinum can be quite variable depending on the composition of the dedifferentiated component. […] The diagnosis is made by demonstrating MDM2 immunostaining of the tumor cells or amplification of MDM2 by FISH, an event that does not occur in true MLS.

• #26 Soft Tissues: Liposarcoma: Myxoid liposarcoma

  https://atlasgeneticsoncology.org/solid-tumor/5169/soft-tissues-liposarcoma-myxoid-liposarcoma

  Liposarcoma is the most common soft tissue malignancy in adults accounting for at least 20% of all sarcomas in this age group. […] Myxoid-round cell liposarcoma is a subtype of liposarcoma characterized by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11). This translocation creates the FUS-DDIT3 chimeric gene. […] Cytogenetics analyses have shown that several lipogenic tumours are characterized by specific chromosomal abnormalities, the best known was the reciprocal translocation t(12;16)(q13;p11) of myxoid-round cell liposarcoma, described about twenty years ago. This translocation results in a fusion gene consisting of the 5 part of the FUS (TLS) gene and the complete coding region of the CHOP gene. […] The involvement of a nuclear riboprotein in these processes in vivo indicates that FUS is important in genome maintenance.

• #27 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  The most prominent cytogenetic feature of MRCL is that about 95% of cases have specific t(12;16)(q13;p11) chromosomal translocation, which produces FUS-DDIT3 fusion protein, while about 5% of cases have t(12;22) (q13;q12) chromosomal translocation, producing EWSR1-DDIT3 fusion protein. […] These fusion proteins are important molecules for development of sarcoma and inhibition of adipogenesis and play crucial roles in the pathogenesis of MRCL. […] The expression level of FUS-DDIT3 fusion protein is also positively correlated with cell differentiation. […] Studies have shown that the FUS-DDIT3 fusion gene can enhance the invasion ability of MRCL by activating the SRC/FAK/RHO/ROCK signal axis, and the expression level of FAK is related to the degree of malignancy and the tumor grade. […] It has been shown that MRCL can cause gene mutation of EGFR, PDGFRB, RET, MET and VEGFR1 through the interaction of the autocrine/paracrine loop and the receptor tyrosine kinase (RTK), and it can keep activating the signaling pathway of the downstream PI3K/Akt, leading to the over-expression of growth factor receptor RET and IGF1R, which is related to the transformation of MLS to RCL, increasing invasiveness, and poor prognosis.

• #28 Liposarcomas of the mediastinum – Suster – Mediastinum

  https://med.amegroups.org/article/view/5725/html

  Myxoid liposarcoma (MLS), on the other hand, follows a different oncogenic mechanism and is characterized by a t(12;16)(q13;p11), which leads to the formation of a fusion oncogene: FUS-DDIT3 (DDIT3 was formerly known as CHOP) in 95% of cases or an EWSR1-DDIT3 in about 5% of cases. […] The role of immunohistochemistry and molecular pathology has been amply studied in these tumors. […] Like WDL, the diagnosis of DDLS is facilitated using antibodies for MDM2, which will show scattered nuclear positivity in the spindle cells of the non-lipogenic component as well as in the neoplastic adipocytic component. […] The histology of DDLS within the mediastinum can be quite variable depending on the composition of the dedifferentiated component. […] The diagnosis is made by demonstrating MDM2 immunostaining of the tumor cells or amplification of MDM2 by FISH, an event that does not occur in true MLS.

• #29 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  Liposarcoma is a complex tumor, and its pathophysiology can be best explained by dividing it into three subtypes (according to the World Health Organization (WHO) classification from 2002). These include well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS), myxoid and round cell liposarcoma (MLS and RCL), and pleomorphic liposarcoma (PLS). WDLPS/DDLPS will have a diagnostic giant marker and ring chromosome, which affects uncontrolled cell proliferation. For MCL and RCL, reciprocal translocation occurs between chromosomes 12 and 16, leading to the fusion of genes DDIT3 and FUS and subsequently activating some downstream targets such as PPARgamma2 and C/EBPalpha, promoting cell cycle proliferation. Pleomorphic liposarcoma is the most complex and least-understood of these. Mutations in various tumor suppressor pathways like p53, NF1, RB1 lead to many gains and account for the aggressive nature of this tumor.

• #30 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  The most prominent cytogenetic feature of MRCL is that about 95% of cases have specific t(12;16)(q13;p11) chromosomal translocation, which produces FUS-DDIT3 fusion protein, while about 5% of cases have t(12;22) (q13;q12) chromosomal translocation, producing EWSR1-DDIT3 fusion protein. […] These fusion proteins are important molecules for development of sarcoma and inhibition of adipogenesis and play crucial roles in the pathogenesis of MRCL. […] The expression level of FUS-DDIT3 fusion protein is also positively correlated with cell differentiation. […] Studies have shown that the FUS-DDIT3 fusion gene can enhance the invasion ability of MRCL by activating the SRC/FAK/RHO/ROCK signal axis, and the expression level of FAK is related to the degree of malignancy and the tumor grade. […] It has been shown that MRCL can cause gene mutation of EGFR, PDGFRB, RET, MET and VEGFR1 through the interaction of the autocrine/paracrine loop and the receptor tyrosine kinase (RTK), and it can keep activating the signaling pathway of the downstream PI3K/Akt, leading to the over-expression of growth factor receptor RET and IGF1R, which is related to the transformation of MLS to RCL, increasing invasiveness, and poor prognosis.

• #31 Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03228-z

  Myxoid liposarcoma (MLPS) is a subtype of liposarcoma. It is characterized by the expression of the FUS-DDIT3 chimeric protein caused by the chromosomal translocation t(12;16)(q13;p11) considered the pathogenic event leading to MLPS development. […] Previous data demonstrate that in MLPS trabectedin allows the reactivation of the adipogenic process overcoming the effect of the chimeric protein. […] Trabectedin modulates these binding sites, particularly after prolonged treatment, resulting in transcriptional re-activation of genes involved in differentiation. […] We do not have an explanation for the finding that trabectedin affects the DNA binding of FUS-DDIT3 in the sensitive ML017 tumor but not in the resistant ML017ET tumor. […] In summary, we revealed trabectedin’s unique mechanism in MLPS by inhibiting the FUS-DDIT3 binding of target genes, removing the differentiation block.

• #32 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  The most prominent cytogenetic feature of MRCL is that about 95% of cases have specific t(12;16)(q13;p11) chromosomal translocation, which produces FUS-DDIT3 fusion protein, while about 5% of cases have t(12;22) (q13;q12) chromosomal translocation, producing EWSR1-DDIT3 fusion protein. […] These fusion proteins are important molecules for development of sarcoma and inhibition of adipogenesis and play crucial roles in the pathogenesis of MRCL. […] The expression level of FUS-DDIT3 fusion protein is also positively correlated with cell differentiation. […] Studies have shown that the FUS-DDIT3 fusion gene can enhance the invasion ability of MRCL by activating the SRC/FAK/RHO/ROCK signal axis, and the expression level of FAK is related to the degree of malignancy and the tumor grade. […] It has been shown that MRCL can cause gene mutation of EGFR, PDGFRB, RET, MET and VEGFR1 through the interaction of the autocrine/paracrine loop and the receptor tyrosine kinase (RTK), and it can keep activating the signaling pathway of the downstream PI3K/Akt, leading to the over-expression of growth factor receptor RET and IGF1R, which is related to the transformation of MLS to RCL, increasing invasiveness, and poor prognosis.

• #33 Myxoid Liposarcoma: Models and Mechanisms of Sarcomagenesis and Response to Radiation Therapy

  https://dukespace.lib.duke.edu/items/4408152b-7045-439a-b5a2-992188d0267b

  Myxoid liposarcoma (MLPS) is a malignant soft tissue sarcoma characterized by a pathognomonic t(12;16)(q13;p11) translocation that produces a fusion oncoprotein, FUS-CHOP. […] However, the mechanism for its radiosensitivity is unknown. In order to further understand the biological mechanisms underlying MLPS response to radiotherapy we studied the fusion oncoprotein FUS-CHOP and linked its role in sarcomagenesis to the radiosensitivity phenotype. […] Here we investigate a molecular mechanism of radiosensitization that couples ionizing radiation to inhibition of translocation-driven sarcomagenesis in myxoid liposarcoma. […] We detected functionally important interactions between FUS-CHOP and multiple chromatin remodeling complexes via co-IP including a new interaction with SNF2H, the ATPase subunit of the imitation switch (ISWI) complex.

• #34 Myxoid Liposarcoma: Models and Mechanisms of Sarcomagenesis and Response to Radiation Therapy

  https://dukespace.lib.duke.edu/items/4408152b-7045-439a-b5a2-992188d0267b

  We further hypothesized that post-translational modification of the FUS-CHOP PrLD may regulate the protein-protein interactions between FUS-CHOP and chromatin remodelers. […] Using irradiated human MLPS cell lines, we show that FUS-CHOP is a target of phosphorylation by the DNA damage response kinases DNA-PK and ATM after irradiation. […] Finally, we show that phosphorylation of the PrLD of FUS-CHOP diminishes protein-protein interactions with chromatin remodeling complexes and the ability for FUS-CHOP to transform NIH-3T3 cells.

• #35

  https://link.springer.com/article/10.1007/s00428-023-03615-5

  Compared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. […] Currently, the underlying mechanism of this particular radiosensitivity is unknown. […] It is postulated that the chimeric fusion product functions as an aberrant transcription factor stimulating proliferation and blocking adipocytic differentiation. […] In general, radiation exerts its effect by damaging DNA and thereby inducing cell cycle arrest, senescence, apoptosis, DNA damage repair and by damaging capillaries and small vessels. […] Notably, MLS showed a low proliferation level, even in the high-grade tumors. This might be explained by the high levels of cyclin-dependent kinase inhibitors found in MLS cells, counteracting growth promoting activity, as it was postulated that the aberrant FUS-DDIT3 transcription factor would result in stimulation of proliferation, while inhibiting adipocytic differentiation.

• #36 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  The cytogenetic feature of PLS is complex aneuploid karyotypes with complex genomic amplification and deletions. […] In general, although many chromosome structures and gene expression abnormalities have been discovered in PLS, no characteristic or constant chromosomal aberrations or molecular alterations have been found. […] With increasing number of studies in molecular basis of pathogenesis and emerging new therapeutic targets, the treatment outcome of liposarcoma will be greatly improved in the future. […] In WDL/DDL, CDK4 is continuously amplified in about 90% of cases, and a CDK4/6 inhibitor, palbociclib, showed certain efficacy in the treatment of advanced CDK4+ WDL/DDL. […] A study reported that the therapeutic effect of CDK4/6 inhibitors on MDL/DDL needed to be achieved by down-regulating the expression of MDM2 protein by PDLIM7 and CDH18.

• #37 Liposarcomas of the mediastinum – Suster – Mediastinum

  https://med.amegroups.org/article/view/5725/html

  The genetic profile of PLS closely resembles that of other high-grade pleomorphic sarcomas, with complex karyotypes and frequent gains of many chromosomal regions. […] PLS does not exhibit amplification of MDM2 or CDK4 and lacks the FUS-DDIT3 or EWSR1-DDIT3 fusion genes. […] Mediastinal liposarcomas comprise a heterogeneous group of tumors with diverse morphology that have the potential for highly aggressive behavior and patient death caused by tumor.

• #38 Liposarcomas of the mediastinum – Suster – Mediastinum

  https://med.amegroups.org/article/view/5725/html

  The genetic profile of PLS closely resembles that of other high-grade pleomorphic sarcomas, with complex karyotypes and frequent gains of many chromosomal regions. […] PLS does not exhibit amplification of MDM2 or CDK4 and lacks the FUS-DDIT3 or EWSR1-DDIT3 fusion genes. […] Mediastinal liposarcomas comprise a heterogeneous group of tumors with diverse morphology that have the potential for highly aggressive behavior and patient death caused by tumor.

• #39 Liposarcomas of the mediastinum – Suster – Mediastinum

  https://med.amegroups.org/article/view/5725/html

  The genetic profile of PLS closely resembles that of other high-grade pleomorphic sarcomas, with complex karyotypes and frequent gains of many chromosomal regions. […] PLS does not exhibit amplification of MDM2 or CDK4 and lacks the FUS-DDIT3 or EWSR1-DDIT3 fusion genes. […] Mediastinal liposarcomas comprise a heterogeneous group of tumors with diverse morphology that have the potential for highly aggressive behavior and patient death caused by tumor.

• #40 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  Liposarcoma is a complex tumor, and its pathophysiology can be best explained by dividing it into three subtypes (according to the World Health Organization (WHO) classification from 2002). These include well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS), myxoid and round cell liposarcoma (MLS and RCL), and pleomorphic liposarcoma (PLS). WDLPS/DDLPS will have a diagnostic giant marker and ring chromosome, which affects uncontrolled cell proliferation. For MCL and RCL, reciprocal translocation occurs between chromosomes 12 and 16, leading to the fusion of genes DDIT3 and FUS and subsequently activating some downstream targets such as PPARgamma2 and C/EBPalpha, promoting cell cycle proliferation. Pleomorphic liposarcoma is the most complex and least-understood of these. Mutations in various tumor suppressor pathways like p53, NF1, RB1 lead to many gains and account for the aggressive nature of this tumor.

• #41

  https://www.orthobullets.com/pathology/8068/liposarcoma

  Liposarcomas are a heterogeneous class of sarcomas with differentiation towards adipose tissue that consist of 5 different sub-types: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. […] the lipoblast (signet ring-type cell) is a hallmark of liposarcomas. […] well-differentiated liposarcoma – amplification (MDM2) […] myxoid liposarcoma – translocation (12;16) […] well-differentiated and dedifferentiated liposarcomas have chromosome 12q13-15 amplification […] pleomorphic liposarcoma may have p53 mutation. […] liposarcoma types are related to the developmental stage of the lipoblasts from which they form […] all are from primitive mesenchymal cells.

• #42 miR-133a function in the pathogenesis of dedifferentiated liposarcoma | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-018-0583-2

  miR-133a was significantly underexpressed in liposarcoma tissues. […] The objective of this study was to characterize the biological and molecular consequences of miR-133a underexpression in DDLPS. […] Based on our collective findings, we propose that in DDPLS, loss of miR-133a induces a metabolic shift due to a reduction in oxidative metabolism favoring a Warburg effect in DDLPS tumors, but this regulation on metabolism was not sufficient to affect DDPLS. […] These data imply miRNAs might act as drivers in the pathogenesis of DDLPS. […] Unexpectedly, we found that several muscle-specific miRNAs (myomiRs), miR-1, -133a, and -206, were significantly underexpressed in liposarcoma compared to their subjacent normal tissues. […] miR-133a might function as a tumor suppressor in human liposarcoma.

• #43 miR-133a function in the pathogenesis of dedifferentiated liposarcoma | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-018-0583-2

  miR-133a was significantly underexpressed in liposarcoma tissues. […] The objective of this study was to characterize the biological and molecular consequences of miR-133a underexpression in DDLPS. […] Based on our collective findings, we propose that in DDPLS, loss of miR-133a induces a metabolic shift due to a reduction in oxidative metabolism favoring a Warburg effect in DDLPS tumors, but this regulation on metabolism was not sufficient to affect DDPLS. […] These data imply miRNAs might act as drivers in the pathogenesis of DDLPS. […] Unexpectedly, we found that several muscle-specific miRNAs (myomiRs), miR-1, -133a, and -206, were significantly underexpressed in liposarcoma compared to their subjacent normal tissues. […] miR-133a might function as a tumor suppressor in human liposarcoma.

• #44 miR-133a function in the pathogenesis of dedifferentiated liposarcoma | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-018-0583-2

  miR-133a overexpression reduced the levels of CTGF in DDLPS cells compared to control vector cells. […] DDLPS cells expressing miR-133a were delayed in entering S phase. […] Together, these results indicate that re-constitution of miR-133a in DDLPS cells promotes a reduction in glycolysis and an increase in OXPHOS. […] These findings suggest the possibility that miR-133a could function as a regulator of oxidative metabolism in DDLPS tumors.

• #45 miR-133a function in the pathogenesis of dedifferentiated liposarcoma | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-018-0583-2

  miR-133a overexpression reduced the levels of CTGF in DDLPS cells compared to control vector cells. […] DDLPS cells expressing miR-133a were delayed in entering S phase. […] Together, these results indicate that re-constitution of miR-133a in DDLPS cells promotes a reduction in glycolysis and an increase in OXPHOS. […] These findings suggest the possibility that miR-133a could function as a regulator of oxidative metabolism in DDLPS tumors.

• #46 miR-133a function in the pathogenesis of dedifferentiated liposarcoma | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-018-0583-2

  miR-133a overexpression reduced the levels of CTGF in DDLPS cells compared to control vector cells. […] DDLPS cells expressing miR-133a were delayed in entering S phase. […] Together, these results indicate that re-constitution of miR-133a in DDLPS cells promotes a reduction in glycolysis and an increase in OXPHOS. […] These findings suggest the possibility that miR-133a could function as a regulator of oxidative metabolism in DDLPS tumors.

• #47 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Exportin-1 mediates nuclear export of multiple tumor suppressor and growth regulatory proteins. Aberrant expression of exportin-1 is noted in human malignancies, resulting in cytoplasmic mislocalization of its target proteins. We investigated the efficacy of selinexor against liposarcoma cells both in vitro and in vivo. Exportin-1 was highly expressed in liposarcoma samples and cell lines as determined by immunohistochemistry, western blot, and immunofluorescence assay. Knockdown of endogenous exportin-1 inhibited proliferation of liposarcoma cells. Selinexor also significantly decreased cell proliferation as well as induced cell cycle arrest and apoptosis of liposarcoma cells. The drug also significantly decreased tumor volumes and weights of liposarcoma xenografts. Importantly, selinexor inhibited insulin-like growth factor 1 (IGF1) activation of IGF-1R/AKT pathway through upregulation of insulin-like growth factor binding protein 5 (IGFBP5).

• #48 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma

  https://escholarship.org/uc/item/80d7d67s

  Exportin-1 mediates nuclear export of multiple tumor suppressor and growth regulatory proteins. Aberrant expression of exportin-1 is noted in human malignancies, resulting in cytoplasmic mislocalization of its target proteins. […] We investigated the efficacy of selinexor against liposarcoma cells both in vitro and in vivo. Exportin-1 was highly expressed in liposarcoma samples and cell lines as determined by immunohistochemistry, western blot, and immunofluorescence assay. Knockdown of endogenous exportin-1 inhibited proliferation of liposarcoma cells. Selinexor also significantly decreased cell proliferation as well as induced cell cycle arrest and apoptosis of liposarcoma cells. The drug also significantly decreased tumor volumes and weights of liposarcoma xenografts. Importantly, selinexor inhibited insulin-like growth factor 1 (IGF1) activation of IGF-1R/AKT pathway through upregulation of insulin-like growth factor binding protein 5 (IGFBP5). Further, overexpression and knockdown experiments showed that IGFBP5 acts as a tumor suppressor and its expression was restored upon selinexor treatment of liposarcoma cells. Selinexor decreased aurora kinase A and B levels in these cells and inhibitors of these kinases suppressed the growth of the liposarcoma cells. Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer.

• #49 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer. […] Present study shows prominent expression of XPO1 protein in different histological subtypes of liposarcoma in patient samples and cell lines compared to benign lipomas. […] These data suggest that robust expression of XPO1 may have a potential role in the pathogenesis or progression of liposarcoma. […] Further, selinexor caused growth inhibition, cell-cycle arrest with upregulation of p21, p27, p53 and downregulation of cyclin B1, cyclin E and survivin. […] Importantly, selinexor (10 mg/kg orally, three times per week at a non-toxic dose) significantly inhibited growth of dedifferentiated liposarcoma (LPS141) xenografts in NSG mice associated with reduced cellular proliferation (Ki-67 staining) and an increase in apoptosis (Tunel staining) in the tumors.

• #50 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer. […] Present study shows prominent expression of XPO1 protein in different histological subtypes of liposarcoma in patient samples and cell lines compared to benign lipomas. […] These data suggest that robust expression of XPO1 may have a potential role in the pathogenesis or progression of liposarcoma. […] Further, selinexor caused growth inhibition, cell-cycle arrest with upregulation of p21, p27, p53 and downregulation of cyclin B1, cyclin E and survivin. […] Importantly, selinexor (10 mg/kg orally, three times per week at a non-toxic dose) significantly inhibited growth of dedifferentiated liposarcoma (LPS141) xenografts in NSG mice associated with reduced cellular proliferation (Ki-67 staining) and an increase in apoptosis (Tunel staining) in the tumors.

• #51 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer. […] Present study shows prominent expression of XPO1 protein in different histological subtypes of liposarcoma in patient samples and cell lines compared to benign lipomas. […] These data suggest that robust expression of XPO1 may have a potential role in the pathogenesis or progression of liposarcoma. […] Further, selinexor caused growth inhibition, cell-cycle arrest with upregulation of p21, p27, p53 and downregulation of cyclin B1, cyclin E and survivin. […] Importantly, selinexor (10 mg/kg orally, three times per week at a non-toxic dose) significantly inhibited growth of dedifferentiated liposarcoma (LPS141) xenografts in NSG mice associated with reduced cellular proliferation (Ki-67 staining) and an increase in apoptosis (Tunel staining) in the tumors.

• #52 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Taken together, these results strongly indicate that inhibition of XPO1 might be a valuable treatment approach for this disease. […] We provide evidence that IGFBP5 can acts as a tumor suppressor in liposarcoma cells in an IGF-1 dependent manner; and selinexor can markedly up-regulate the expression of this tumor suppressor protein. […] We showed that selinexor can significantly decrease levels of aurora-A and aurora-B mRNA. Also, inhibition of aurora kinases either through siRNA or selective inhibitors of aurora-A and aurora-B suppressed the cell growth of liposarcoma cells in both liquid culture and soft agar associated with decreased cyclin B1 and increased expression of tumor suppressor proteins, p53, p27, and p21.

• #53 OhioLINK ETD: Zewdu, Abeba

  https://rave.ohiolink.edu/etdc/view?acc_num=osu15320904714479

  Understanding the pathobiological drivers of dedifferentiated liposarcoma (DDLPS) is imperative for efficacious therapies to eventuate. […] The proclivity of these tumors to occur and reoccur in the high-fat retroperitoneum warrants investigating the setting created by adipose. […] IL6 trans-signaling, in which IL6 cytokine binds to soluble IL6R (sIL6Ra) and activates glycoprotein 130 (GP130) signal transduction, may be critically involved in chronic diseases having an inflammatory component. […] The overall goal of our study was to investigate the role of GP130 as a driver of DDLPS and to evaluate preadipocyte cells as potential IL6 sources. […] Activation of GP130 by IL6 (10 ng/mL) increased DDLPS growth, migration, and induced STAT1 and STAT3 phosphorylation. […] Moreover, GP130 signal transduction induced MDM2 expression three- and ten-fold in DDLPS cell lines Lipo246 and Lipo815, respectively.

• #54 OhioLINK ETD: Zewdu, Abeba

  https://rave.ohiolink.edu/etdc/view?acc_num=osu15320904714479

  Understanding the pathobiological drivers of dedifferentiated liposarcoma (DDLPS) is imperative for efficacious therapies to eventuate. […] The proclivity of these tumors to occur and reoccur in the high-fat retroperitoneum warrants investigating the setting created by adipose. […] IL6 trans-signaling, in which IL6 cytokine binds to soluble IL6R (sIL6Ra) and activates glycoprotein 130 (GP130) signal transduction, may be critically involved in chronic diseases having an inflammatory component. […] The overall goal of our study was to investigate the role of GP130 as a driver of DDLPS and to evaluate preadipocyte cells as potential IL6 sources. […] Activation of GP130 by IL6 (10 ng/mL) increased DDLPS growth, migration, and induced STAT1 and STAT3 phosphorylation. […] Moreover, GP130 signal transduction induced MDM2 expression three- and ten-fold in DDLPS cell lines Lipo246 and Lipo815, respectively.

• #55 OhioLINK ETD: Zewdu, Abeba

  https://rave.ohiolink.edu/etdc/view?acc_num=osu15320904714479

  Loss of GP130 signaling decreased DDLPS tumor cell growth and MDM2 levels. […] Taken together, these data suggest that preadipocytes may act as in situ sources of IL6 for retroperitoneal DDLPS, and that IL6 activation of GP130 may promote the DDLPS oncogenic phenotype via activation of STAT1 and STAT3, and upregulation of MDM2.

• #56 OhioLINK ETD: Zewdu, Abeba

  https://rave.ohiolink.edu/etdc/view?acc_num=osu15320904714479

  Loss of GP130 signaling decreased DDLPS tumor cell growth and MDM2 levels. […] Taken together, these data suggest that preadipocytes may act as in situ sources of IL6 for retroperitoneal DDLPS, and that IL6 activation of GP130 may promote the DDLPS oncogenic phenotype via activation of STAT1 and STAT3, and upregulation of MDM2.

• #57 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20190514/Different-levels-of-two-molecules-from-same-family-can-influence-prognosis-of-liposarcoma.aspx

  High levels of TIMP-1 lead to a poor prognosis while high TIMP-4 indicates a less severe form of liposarcoma. […] This study, published in Carcinogenesis 10th May 2019, described the molecules’ mechanism of action through the YAP/TAZ pathway. […] The mechanism behind the molecules’ behavior in liposarcoma is the activation or suppression of a pathway that is important for cell proliferation: the YAP/TAZ pathway. YAP/TAZ are proteins that promote cell proliferation and are activated in liposarcoma, especially in dedifferentiated type. TIMP-1 activates this pathway, which leads to tumor growth and spread, while TIMP-4 suppresses the pathway. In this study, the research team showed TIMP-1 promotes dedifferentiated liposarcoma cell proliferation through the YAP/TAZ pathway. […] Understanding this mechanism can lead to new therapeutics, such as targeting TIMP-1 or increasing the amount of TIMP-4 in the cancer cells, speculates Ando.

• #58 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20190514/Different-levels-of-two-molecules-from-same-family-can-influence-prognosis-of-liposarcoma.aspx

  High levels of TIMP-1 lead to a poor prognosis while high TIMP-4 indicates a less severe form of liposarcoma. […] This study, published in Carcinogenesis 10th May 2019, described the molecules’ mechanism of action through the YAP/TAZ pathway. […] The mechanism behind the molecules’ behavior in liposarcoma is the activation or suppression of a pathway that is important for cell proliferation: the YAP/TAZ pathway. YAP/TAZ are proteins that promote cell proliferation and are activated in liposarcoma, especially in dedifferentiated type. TIMP-1 activates this pathway, which leads to tumor growth and spread, while TIMP-4 suppresses the pathway. In this study, the research team showed TIMP-1 promotes dedifferentiated liposarcoma cell proliferation through the YAP/TAZ pathway. […] Understanding this mechanism can lead to new therapeutics, such as targeting TIMP-1 or increasing the amount of TIMP-4 in the cancer cells, speculates Ando.

• #59 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20190514/Different-levels-of-two-molecules-from-same-family-can-influence-prognosis-of-liposarcoma.aspx

  High levels of TIMP-1 lead to a poor prognosis while high TIMP-4 indicates a less severe form of liposarcoma. […] This study, published in Carcinogenesis 10th May 2019, described the molecules’ mechanism of action through the YAP/TAZ pathway. […] The mechanism behind the molecules’ behavior in liposarcoma is the activation or suppression of a pathway that is important for cell proliferation: the YAP/TAZ pathway. YAP/TAZ are proteins that promote cell proliferation and are activated in liposarcoma, especially in dedifferentiated type. TIMP-1 activates this pathway, which leads to tumor growth and spread, while TIMP-4 suppresses the pathway. In this study, the research team showed TIMP-1 promotes dedifferentiated liposarcoma cell proliferation through the YAP/TAZ pathway. […] Understanding this mechanism can lead to new therapeutics, such as targeting TIMP-1 or increasing the amount of TIMP-4 in the cancer cells, speculates Ando.

• #60 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  The cause of liposarcoma is still unknown. The American Cancer Society has identified some apparent risk factors for soft tissue sarcomas; however, multiple cases exist where patients have no apparent risk factors for the disease. The exact genetic mutation leading to these malignancies is still under investigation. Liposarcoma risk factors identified by the American Cancer Society include radiation (especially radiation therapy used to treat other malignancies), certain family cancer syndromes, damage/trauma to the lymphatic system, and exposure to toxic chemicals. It is important to note that liposarcomas do not develop from lipomas, which are completely benign.

• #61 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  The cause of liposarcoma is still unknown. The American Cancer Society has identified some apparent risk factors for soft tissue sarcomas; however, multiple cases exist where patients have no apparent risk factors for the disease. The exact genetic mutation leading to these malignancies is still under investigation. Liposarcoma risk factors identified by the American Cancer Society include radiation (especially radiation therapy used to treat other malignancies), certain family cancer syndromes, damage/trauma to the lymphatic system, and exposure to toxic chemicals. It is important to note that liposarcomas do not develop from lipomas, which are completely benign.

• #62 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  The cause of liposarcoma is still unknown. The American Cancer Society has identified some apparent risk factors for soft tissue sarcomas; however, multiple cases exist where patients have no apparent risk factors for the disease. The exact genetic mutation leading to these malignancies is still under investigation. Liposarcoma risk factors identified by the American Cancer Society include radiation (especially radiation therapy used to treat other malignancies), certain family cancer syndromes, damage/trauma to the lymphatic system, and exposure to toxic chemicals. It is important to note that liposarcomas do not develop from lipomas, which are completely benign.

• #63 Liposarcoma: Symptoms, Causes, Stages, Diagnosis and Treatment – OncoDaily

  https://oncodaily.com/oncolibrary/cancer-types/liposarcoma

  Liposarcoma is primarily driven by genetic mutations, though the exact causes of these alterations remain under investigation. Key risk factors include prior exposure to radiation therapy, certain chemicals like vinyl chloride, and inherited genetic conditions. […] A significant number of liposarcomas exhibit amplification of the MDM2 gene, which encodes a protein that regulates the tumor suppressor p53. This amplification leads to increased MDM2 protein levels, resulting in the degradation of p53 and promoting tumor growth. […] Many liposarcomas also show amplification of the CDK4 gene, leading to overexpression of the CDK4 protein, which drives cell cycle progression and contributes to tumor development. […] These genetic alterations are particularly prevalent in well-differentiated and dedifferentiated liposarcomas, underscoring their role in the diseases pathogenesis.

• #64 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  The cause of liposarcoma is still unknown. The American Cancer Society has identified some apparent risk factors for soft tissue sarcomas; however, multiple cases exist where patients have no apparent risk factors for the disease. The exact genetic mutation leading to these malignancies is still under investigation. Liposarcoma risk factors identified by the American Cancer Society include radiation (especially radiation therapy used to treat other malignancies), certain family cancer syndromes, damage/trauma to the lymphatic system, and exposure to toxic chemicals. It is important to note that liposarcomas do not develop from lipomas, which are completely benign.

• #65 Liposarcoma

  https://dermnetnz.org/topics/liposarcoma

  LPS arises de novo rather than from a pre-existing lipoma. […] Unlike other soft tissue sarcomas, radiation does not appear to play a role in pathogenesis. […] The genetics of LPS vary based on the type of liposarcoma: WDLPS and DDLPS: characterised by recurrent amplifications within chromosome 12, resulting in over-expression of oncogenic genes; MLPS is characterised by a pathognomonic chromosomal translocation between chromosomes 12 and 16, resulting in an oncogenic fusion protein (FUS-DDIT3); PLPS is karyotypically complex, with a variety of mutations present.

• #66 Liposarcoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1102007-overview

  Liposarcoma is a lipogenic tumor of large deep-seated connective tissue spaces. Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer development. An abnormality of band 12q13 has been associated with the development of liposarcomas. The most common chromosomal translocation is the FUS-CHOP fusion gene, which encodes a transcription factor necessary for adipocyte differentiation. These and other distinct genetic aberrations may aid in the diagnosis of particular liposarcoma subtypes, and they can potentially be targets that can be exploited therapeutically. […] The development of a liposarcoma from a preexisting benign lipoma is rare. Most cases arise de novo. Liposarcomas most frequently arise from the deep-seated stroma rather than the submucosal or subcutaneous fat.

• #67

  https://www.orthobullets.com/pathology/8068/liposarcoma

  Liposarcomas are a heterogeneous class of sarcomas with differentiation towards adipose tissue that consist of 5 different sub-types: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. […] the lipoblast (signet ring-type cell) is a hallmark of liposarcomas. […] well-differentiated liposarcoma – amplification (MDM2) […] myxoid liposarcoma – translocation (12;16) […] well-differentiated and dedifferentiated liposarcomas have chromosome 12q13-15 amplification […] pleomorphic liposarcoma may have p53 mutation. […] liposarcoma types are related to the developmental stage of the lipoblasts from which they form […] all are from primitive mesenchymal cells.

• #68

  https://www.orthobullets.com/pathology/8068/liposarcoma

  Liposarcomas are a heterogeneous class of sarcomas with differentiation towards adipose tissue that consist of 5 different sub-types: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. […] the lipoblast (signet ring-type cell) is a hallmark of liposarcomas. […] well-differentiated liposarcoma – amplification (MDM2) […] myxoid liposarcoma – translocation (12;16) […] well-differentiated and dedifferentiated liposarcomas have chromosome 12q13-15 amplification […] pleomorphic liposarcoma may have p53 mutation. […] liposarcoma types are related to the developmental stage of the lipoblasts from which they form […] all are from primitive mesenchymal cells.

• #69 Primary pleomorphic liposarcoma of the liver: a case report and literature review | Surgical Case Reports | Full Text

  https://surgicalcasereports.springeropen.com/articles/10.1186/s40792-021-01322-4

  Primary liposarcoma arising from the liver is exceedingly rare. […] In addition, we discuss theories regarding pathogenesis and the pathological and clinical features of primary hepatic liposarcoma to better outline this rare entity. […] The source of adipocytic cells in primary hepatic liposarcoma is unclear. Hepatic mesenchymal stem cells (MSCs), circulating MSCs, and hepatic progenitor cells (HPCs) are potential alternative origins. […] Despite comprising a minuscule fraction of liver cells, hepatic MSCs serve as potential cells of origin for primary hepatic liposarcoma due to their multipotency. […] Theoretically, liver damage can trigger circulating MSC migration, and abnormal adipocytic differentiation may form hepatic liposarcoma. […] The findings from our patient support hepatic MSCs, circulating MSCs, or HPCs as possible cells of origin for primary hepatic liposarcoma, although definitive etiology cannot be determined from these results alone.

• #70 Primary pleomorphic liposarcoma of the liver: a case report and literature review | Surgical Case Reports | Full Text

  https://surgicalcasereports.springeropen.com/articles/10.1186/s40792-021-01322-4

  Primary liposarcoma arising from the liver is exceedingly rare. […] In addition, we discuss theories regarding pathogenesis and the pathological and clinical features of primary hepatic liposarcoma to better outline this rare entity. […] The source of adipocytic cells in primary hepatic liposarcoma is unclear. Hepatic mesenchymal stem cells (MSCs), circulating MSCs, and hepatic progenitor cells (HPCs) are potential alternative origins. […] Despite comprising a minuscule fraction of liver cells, hepatic MSCs serve as potential cells of origin for primary hepatic liposarcoma due to their multipotency. […] Theoretically, liver damage can trigger circulating MSC migration, and abnormal adipocytic differentiation may form hepatic liposarcoma. […] The findings from our patient support hepatic MSCs, circulating MSCs, or HPCs as possible cells of origin for primary hepatic liposarcoma, although definitive etiology cannot be determined from these results alone.

• #71 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  In DDL, many other potential therapeutic targets have been reported. […] Immune checkpoint inhibitors have opened up a new way for the treatment of DDL. […] The core role of miR-143 in the occurrence and development of WDL/DDL has been confirmed. […] The aforementioned miRNA with tumor-suppressing function are good indicators of efficacy evaluation and prognosis, as well as potential therapeutic targets. […] In the past decade, an in-depth research on the cellular and molecular pathogenesis of liposarcoma has brought about new ideas and methods for clinical diagnosis, treatment and prognosis.

• #72 Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment

  https://www.jcancer.org/v11p0100.htm

  In DDL, many other potential therapeutic targets have been reported. […] Immune checkpoint inhibitors have opened up a new way for the treatment of DDL. […] The core role of miR-143 in the occurrence and development of WDL/DDL has been confirmed. […] The aforementioned miRNA with tumor-suppressing function are good indicators of efficacy evaluation and prognosis, as well as potential therapeutic targets. […] In the past decade, an in-depth research on the cellular and molecular pathogenesis of liposarcoma has brought about new ideas and methods for clinical diagnosis, treatment and prognosis.

• #73 Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03228-z

  The marine drug trabectedin has shown unusual effectiveness in the treatment of myxoid liposarcoma (MLPS), a liposarcoma characterized by the expression of the FUS-DDIT3 chimera. […] However, the role of the chimeric protein in the mechanism of action of the drug is not entirely understood. […] Through ChIP-Seq, here we demonstrate that trabectedin inhibits the binding of FUS-DDIT3 to its target genes, restoring adipocyte differentiation in a patient-derived xenograft model of MLPS sensitive to trabectedin. […] These findings explain the unusual mechanism underlying trabectedin’s effectiveness against MLPS by pinpointing the chimera’s role in inducing the differentiation block responsible for MLPS pathogenesis. […] Trabectedin is a marine drug known to have a pleiotropic mechanism of action.

• #74 Mechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites | Journal of Experimental & Clinical Cancer Research | Full Text

  https://jeccr.biomedcentral.com/articles/10.1186/s13046-024-03228-z

  Myxoid liposarcoma (MLPS) is a subtype of liposarcoma. It is characterized by the expression of the FUS-DDIT3 chimeric protein caused by the chromosomal translocation t(12;16)(q13;p11) considered the pathogenic event leading to MLPS development. […] Previous data demonstrate that in MLPS trabectedin allows the reactivation of the adipogenic process overcoming the effect of the chimeric protein. […] Trabectedin modulates these binding sites, particularly after prolonged treatment, resulting in transcriptional re-activation of genes involved in differentiation. […] We do not have an explanation for the finding that trabectedin affects the DNA binding of FUS-DDIT3 in the sensitive ML017 tumor but not in the resistant ML017ET tumor. […] In summary, we revealed trabectedin’s unique mechanism in MLPS by inhibiting the FUS-DDIT3 binding of target genes, removing the differentiation block.

• #75 Histology driven systemic therapy of liposarcoma—ready for prime time? – Grethlein – Translational Gastroenterology and Hepatology

  https://tgh.amegroups.org/article/view/4712/html

  The mechanism has been proposed to be functional inactivation of the oncogenic chimera FUS-CHOP, with a downstream impact on adipocyte differentiation. The authors studying this mechanism commented that To our knowledge this is the first report indicating that a small molecule can displace an oncogenic transcription factor in vivo from its target DNA sequences, thus specifically modulating the transcription of genes involved in the pathogenesis of a neoplastic disease. […] WDLPS and DDLPS have amplification of CDK4 in 90% of cases. A clinical trial of 60 WDLPS or DDLPS patients treated with palbociclib, an oral CDK4 and CDK6 inhibitor, at the doses approved by the FDA for the treatment of patients with breast cancer125 mg daily for 21 out of 28 days. […] The original phase II trial of pazopanib in soft tissue sarcomas revealed minimal activity in liposarcomas. […] The one exception is the myxoid/round cell liposarcoma subgroup.

• #76 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer. […] Present study shows prominent expression of XPO1 protein in different histological subtypes of liposarcoma in patient samples and cell lines compared to benign lipomas. […] These data suggest that robust expression of XPO1 may have a potential role in the pathogenesis or progression of liposarcoma. […] Further, selinexor caused growth inhibition, cell-cycle arrest with upregulation of p21, p27, p53 and downregulation of cyclin B1, cyclin E and survivin. […] Importantly, selinexor (10 mg/kg orally, three times per week at a non-toxic dose) significantly inhibited growth of dedifferentiated liposarcoma (LPS141) xenografts in NSG mice associated with reduced cellular proliferation (Ki-67 staining) and an increase in apoptosis (Tunel staining) in the tumors.

• #77 Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma | Oncotarget

  https://www.oncotarget.com/article/13485/text/

  Taken together, these results strongly indicate that inhibition of XPO1 might be a valuable treatment approach for this disease. […] We provide evidence that IGFBP5 can acts as a tumor suppressor in liposarcoma cells in an IGF-1 dependent manner; and selinexor can markedly up-regulate the expression of this tumor suppressor protein. […] We showed that selinexor can significantly decrease levels of aurora-A and aurora-B mRNA. Also, inhibition of aurora kinases either through siRNA or selective inhibitors of aurora-A and aurora-B suppressed the cell growth of liposarcoma cells in both liquid culture and soft agar associated with decreased cyclin B1 and increased expression of tumor suppressor proteins, p53, p27, and p21.

• #78 Liposarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538265/

  Liposarcoma is a complex tumor, and its pathophysiology can be best explained by dividing it into three subtypes (according to the World Health Organization (WHO) classification from 2002). These include well-differentiated and dedifferentiated liposarcoma (WDLPS/DDLPS), myxoid and round cell liposarcoma (MLS and RCL), and pleomorphic liposarcoma (PLS). WDLPS/DDLPS will have a diagnostic giant marker and ring chromosome, which affects uncontrolled cell proliferation. For MCL and RCL, reciprocal translocation occurs between chromosomes 12 and 16, leading to the fusion of genes DDIT3 and FUS and subsequently activating some downstream targets such as PPARgamma2 and C/EBPalpha, promoting cell cycle proliferation. Pleomorphic liposarcoma is the most complex and least-understood of these. Mutations in various tumor suppressor pathways like p53, NF1, RB1 lead to many gains and account for the aggressive nature of this tumor.

• #79 Frontiers | Targeting liposarcoma: unveiling molecular pathways and therapeutic opportunities

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1484027/full

  In recent years, an increasing number of studies have utilized molecular biology techniques to reveal important molecular heterogeneity among different subtypes of liposarcoma. Each subtype exhibits distinct genetic patterns and molecular pathways, which may serve as important targets for molecular therapy. […] In the present review, we discuss the molecular characteristics, molecular diagnostics, driver genes, and molecular pathogenesis of LPS. We also explore the corresponding therapeutic targets and downstream pathways, and summarize progress toward targeted therapies for several subtypes of LPS. […] The generation of different LPS subtypes is caused by their relatively unique driver genes and molecular mechanisms, which ultimately lead to large differences between subtypes. […] Progress in research into driver genes and molecular pathways has elucidated the mechanisms of LPS in a stepwise manner. These studies have also provided insights and guidance regarding the content and direction of clinical research.

• #80 Liposarcoma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/liposarcoma/symptoms-causes/syc-20352632

  Liposarcoma starts when fat cells get changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. The changes turn the fat cells into cancer cells. The changes tell the cancer cells to grow quickly and make a lot of extra cells. The cancer cells keep living when healthy cells would die as part of their natural life cycle. […] The cancer cells form a growth, called a tumor. In some types of liposarcoma, the cancer cells stay put. They continue making more cells, causing the tumor to get bigger. In other types of liposarcoma, the cancer cells might break away and spread to other parts of the body. When cancer spreads to other parts of the body, it’s called metastatic cancer.

• #81 Liposarcoma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/liposarcoma/symptoms-causes/syc-20352632

  Liposarcoma starts when fat cells get changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. The changes turn the fat cells into cancer cells. The changes tell the cancer cells to grow quickly and make a lot of extra cells. The cancer cells keep living when healthy cells would die as part of their natural life cycle. […] The cancer cells form a growth, called a tumor. In some types of liposarcoma, the cancer cells stay put. They continue making more cells, causing the tumor to get bigger. In other types of liposarcoma, the cancer cells might break away and spread to other parts of the body. When cancer spreads to other parts of the body, it’s called metastatic cancer.

• #82 Liposarcoma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/liposarcoma/symptoms-causes/syc-20352632

  Liposarcoma starts when fat cells get changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. The changes turn the fat cells into cancer cells. The changes tell the cancer cells to grow quickly and make a lot of extra cells. The cancer cells keep living when healthy cells would die as part of their natural life cycle. […] The cancer cells form a growth, called a tumor. In some types of liposarcoma, the cancer cells stay put. They continue making more cells, causing the tumor to get bigger. In other types of liposarcoma, the cancer cells might break away and spread to other parts of the body. When cancer spreads to other parts of the body, it’s called metastatic cancer.

• #83 Frontiers | Targeting liposarcoma: unveiling molecular pathways and therapeutic opportunities

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1484027/full

  In recent years, an increasing number of studies have utilized molecular biology techniques to reveal important molecular heterogeneity among different subtypes of liposarcoma. Each subtype exhibits distinct genetic patterns and molecular pathways, which may serve as important targets for molecular therapy. […] In the present review, we discuss the molecular characteristics, molecular diagnostics, driver genes, and molecular pathogenesis of LPS. We also explore the corresponding therapeutic targets and downstream pathways, and summarize progress toward targeted therapies for several subtypes of LPS. […] The generation of different LPS subtypes is caused by their relatively unique driver genes and molecular mechanisms, which ultimately lead to large differences between subtypes. […] Progress in research into driver genes and molecular pathways has elucidated the mechanisms of LPS in a stepwise manner. These studies have also provided insights and guidance regarding the content and direction of clinical research.

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