Materiały źródłowe

• #1 Chondrosarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538132/

  Chondrosarcomas are malignant cartilaginous neoplasms with diverse morphological features and clinical behavior. They account for about 20 percent of all primary malignant tumors of the bone and usually arise in the pelvis or long bones. Primary or conventional chondrosarcoma arises in preexisting normal bone and is distinguished from the rarer secondary tumors, which occur within a preexisting enchondroma or osteochondroma. […] The majority of chondrosarcomas are sporadic, but they may develop from the malignant transformation of osteochondromas and enchondromas. Malignant transformation occurs in 5% of osteochondromas either multiple or solitary forms. […] Chromosomal anomalies detected in some types of chondrosarcomas include 9p21, 10, 13q14, and 17p13. Chromosomal structural abnormalities and genetic instability are reported in well-differentiated chondrosarcomas analyzed by cytogenetics. Moreover, the amplification of MYC and AP-1 transcription factors plays a vital role in the pathogenesis of chondrosarcoma.

• #2 Chondrosarcoma | Oncohema Key

  https://oncohemakey.com/chondrosarcoma-3/

  Chondrosarcomas constitute a heterogeneous group of malignant cartilaginous matrix-producing bone neoplasms with diverse morphologic features and clinical behavior. Following osteosarcoma, chondrosarcoma is the second most common primary bone tumor, accounting for 20% to 27% of primary bone malignancy. […] Chondrosarcomas that arise de novo are called primary chondrosarcomas, while those superimposed on preexisting cartilaginous neoplasms such as enchondroma or osteochondroma are referred to as secondary chondrosarcomas. […] The cornerstone of the management of localized chondrosarcomas is surgical resection. […] Many patients will eventually develop metastatic disease, which is nearly uniformly fatal in the absence of effective systemic therapy. […] The clinical challenge is to prevent recurrence and to find better treatment options for unresectable or metastatic disease.

• #3

  https://www.orthobullets.com/pathology/8023/chondrosarcoma

  Chondrosarcoma is the second most common malignant primary bone tumor. These cancers are composed of malignant chondrocytes. There are various subtypes of chondrosarcoma, each with unique characteristics. „Conventional” chondrosarcoma accounts for 90% of chondrosarcomas and typically presents in adults over 40 with progressive pain. […] Diagnosis is made by correlating clinical and imaging (x-ray, CT, MRI) findings with lesional biopsy showing malignant cartilage that permeates and entraps pre-existing bone trabeculae. […] Majority of chondrosarcomas are sporadic (primary chondrosarcomas), but they may develop from the malignant transformation of osteochondromas or enchondromas (secondary chondrosarcomas). […] Mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) identified in primary and secondary conventional chondrosarcomas and enchondromas.

• #4 Chondrosarcoma: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1258236-overview

  Chondrosarcomas may be divided into primary and secondary lesions on the basis of their origins. Primary chondrosarcomas arise de novo, whereas secondary chondrosarcomas arise from preexisting lesions of the cartilage. […] Except for their origin in preexisting cartilaginous conditions, secondary chondrosarcomas are similar to conventional chondrosarcomas in all respects. In addition, the genes responsible for the lesions depend on the primary benign cartilaginous condition. Secondary chondrosarcomas occur in individuals with Ollier disease, Maffucci syndrome, multiple hereditary exostosis (diaphyseal aclasis), solitary osteochondroma, solitary enchondroma, solitary periosteal enchondroma, Paget disease, or radiation injury. […] Amplification of the c-myc proto-oncogene and fos/jun has been implicated in the pathogenesis of chondrosarcoma.

• #5 Chondrosarcoma pathophysiology – wikidoc

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

  The exact pathogenesis of chondrosarcoma is not fully understood. Multiple genes have been implicated in pathogenesis of chondrosarcoma. […] Cytogenetic analysis of chondrosarcomas revealed that structural abnormalities of chromosomes 1, 6, 9, 12 and 15. […] Also, numerical abnormalities of chromosomes 5, 7, 8 and 18 were most frequent associated with chondrosarcoma. […] Anomalies associated with chromosome 9(9p12-22) are more commonly seen in central chondrosarcomas. […] Patients with multiple osteochondromas seem to have germline mutations in the exostosin (EXT1 or EXT2) genes. […] This result is decreased EXT expression and decreased biosynthesis and release of heparan sulfate proteoglycans (HSPGs), which are essential for cell signaling through IHH/PTHLH pathways. […] This in turn decreases normal chondrocyte proliferation and differentiation within the normal human growth plate.

• #6 Chondrosarcoma-from Molecular Pathology to Novel Therapies

  https://www.mdpi.com/2072-6694/13/10/2390

  Chondrosarcoma (CHS) is the second most common primary malignant bone sarcoma. […] We summarized the most frequently mutated genes and genome regions with altered pathways involved in the pathology of this tumor. […] One of the most common point mutations occurs in IDH1 and isocitrate dehydrogenase 2 (IDH2) genes. […] IDH1/2 mutations are also documented in cartilaginous neoplasms, including approximately 50% of patients with CHS (65% of conventional CHSs and up to 57% of dedifferentiated CHSs). […] The presence of IDH mutations can also be used in differential diagnostic between dedifferentiated CHS and undifferentiated pleomorphic sarcoma of bone (UPS) or high-grade CHS and chondroblastic osteosarcoma, where UPS and chondroblastic osteosarcoma lack IDH1/2 mutations. […] The second most frequent mutation in conventional (central and peripheral) and dedifferentiated CHS occurs in the TP53 gene (20–50%).

• #7 Chondrosarcoma information pack – RareCan

  https://rarecan.com/about/rare-cancer-list/chondrosarcoma/chondrosarcoma-information-pack/

  Chondrosarcoma forms when chondrocytes begin to divide uncontrollably leading to the development of a tumour. […] The most common mutation in chondrosarcoma in a gene called IDH1. 50-58% of conventional type chondrosarcomas have this mutation or one in a similar gene called IDH2. […] This mutant gene leads to the production of a chemical that isn’t normally found in cells, called 2-HG that affects the way DNA behaves, making tumours more likely. […] Another gene change that is associated with chondrosarcoma is unique to the mesenchymal form, although it has been seen in other cancers. It is called a HEY1:NCOA2 fusion and is common enough in mesenchymal chondrosarcoma (up to 80% of cases) that the NHS will use a genetic test for it to confirm a diagnosis. […] These new genes make new proteins combining features of the original ones that together can change how a cell behaves and sometimes lead to cancer. […] The final chondrosarcoma genetic change that can be tested for is for the extraskeletal myxoid chondrosarcomas. These have another fusion where a gene called NR4A3 gets fused to one of several different genes, again creating new proteins that aid the development of cancer.

• #8 Understanding chondrosarcoma: symptoms, treatment and prognosis | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/understanding-chondrosarcoma–symptoms–treatment-and-prognosis.h00-159699123.html

  Its not known what exactly causes chondrosarcoma. […] We think sometimes cells in the bone get reprogrammed for reasons that are not clearly understood, says Conley. […] An MD Anderson study published in 2023 found that patients with conventional and dedifferentiated chondrosarcoma who have the TP53 gene mutation have a poorer prognosis. […] But what weve proven through research is that the TP53 mutation can help determine prognosis as well. This helps us counsel patients during treatment.

• #9

  https://link.springer.com/article/10.1007/s40487-024-00317-z

  The pathogenesis of chondrosarcomas can be broadly divided into genetic mutations causing epigenetic modifications and signalling pathway dysregulation. […] Genetic mutations in COL2A1, CDKN2A and TP53 and signalling pathway dysregulation have been implicated in the carcinogenesis of chondrosarcoma. […] Hypermethylation-driven uncontrolled cell proliferation and resistance to apoptosis through mutations in the enzyme isocitrate dehydrogenase (IDH) is also increasingly being recognized to play a pivotal role in the oncogenesis of chondrosarcoma. […] Given the central role of mutant IDH in producing 2-HG, the inhibition of mutant IDH enzymes represents a promising therapeutic strategy. […] The initiation of carcinogenesis via the hedgehog pathway begins with hedgehog ligands binding to the patched receptor (PTCH1), which activates a transmembrane protein called smoothened (SMO). These SMO proteins go on to activate transcription factors that drive cell growth, proliferation and survival. In chondrosarcoma, it is often the overexpression of hedgehog ligands, mutations in PTCH1 or SMO that drive aggressive tumour behaviour. Hence, directly inhibiting the SMO protein is thought to prevent downstream hedgehog signalling.

• #10 Central Chondrosarcoma, Grades 2 and 3 – SFA

  https://curesarcoma.org/sarcoma-subtypes/central-chondrosarcoma-grades-2-and-3/

  About half of these tumors carry IDH1 or IDH2 mutations, suggesting that they have progressed from enchondroma and ACT/CS1. […] Grade 2 and 3 central chondrosarcomas are characterized by aneuploidy and complex karyotypes. […] Polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of progression in a subset. […] Alterations in the p53 and RB1 signaling pathways are involved in tumor progression; the RB1 pathway is affected in 86% of high-grade chondrosarcomas, including by loss of p16 and overexpression and/or amplification of CDK4. […] TP53 is mutated in 20–49% of the cases, whereas mutations in CDKN2A (encoding p16) are infrequent. […] For central chondrosarcoma, several active signaling pathways have been identified, which might provide novel treatment options, such as hedgehog signaling, mTOR signaling, SRC and AKT, and metabolic pathways. […] Members of the BCL2 family seem to play an important role in the chemoresistance of chondrosarcoma.

• #11 Chondrosarcoma-from Molecular Pathology to Novel Therapies

  https://www.mdpi.com/2072-6694/13/10/2390

  High expression of CDK4 and MDM2 is associated with amplification in the 12q13 gene region, which was often observed in central CHS and correlated with higher histological grade of this tumor. […] The differentiation of CHS among other bone neoplasms is complex and based primarily on analysis of radiological images, clinical data, and evaluation of histological or molecular markers. […] The role of the Hh pathway in CHS was also detected by Xiang et al. […] The failures of clinical studies may be explained by occurring with PTCH or SMO mutation, which results in ligand-independent activation of the Hh pathway in CHS.

• #12

  https://www.orthobullets.com/pathology/8023/chondrosarcoma

  Mesenchymal chondrosarcomas are characterized by HEY1-NCOA2 fusion protein. […] Dedifferentiated chondrosarcoma is characterized by a bimorphic histology, with a low grade chondrosarcoma component adjacent to a high grade spindle cell component (usually osteosarcoma, fibrosarcoma, MFH). […] Increased telomerase activity has been shown to directly correlate with the rate of recurrence.

• #13 Chondrosarcoma pathophysiology – wikidoc

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

  Low-grade chondrosarcomas are near-diploid and have very few karyotypic abnormalities. […] On the other hand, high grade chondrosarcomas are aneuploid and have complex karyotypes. […] The progression of chondrosarcoma has been linked to the CDKN2A (p16) tumor suppressor gene present at 9p21 and by mutation in p53. […] Mutations in COL2A1 have also been hypothesized in pathogenesis of chondrosarcomas. […] In addition, amplification of the c-myc and fos/jun protein has also been implicated in the pathogenesis of chondrosarcoma. […] A specific HEY1-NCOA2 fusion product due to an intra-chromosomal rearrangement of chromosome arm 8q result in mesenchymal chondrosarcoma. […] With extraskeletal myxoid chondrosarcomas, the t(9;22)(q22;q12) translocation is common.

• #14 Understanding the Role of IDH Mutation in Chondrosarcoma – University of Miami

  https://scholarship.miami.edu/esploro/outputs/doctoral/Understanding-the-Role-of-IDH-Mutation/991031447192702976

  Chondrosarcomas constitute a heterogeneous group of malignant bone tumors that produce hyaline cartilaginous matrix. […] Mutations in isocitrate dehydrogenase 1/2 (IDH1/2) enzymes were recently described in several malignancies including conventional and dedifferentiated chondrosarcomas. These mutations represent a novel genetic abnormality in chondrosarcoma, indicating a potential role for aberrant IDH function in the pathogenesis of this malignancy. IDH mutations lead to the inability of IDH to convert isocitrate into α-ketoglutarate (α-KG). Instead, α-KG is reduced into D-2-hydroxyglutarate (D-2HG), an oncometabolite. IDH mutations have been shown to initiate tumorigenesis by D-2HG acting as a competitive inhibitor of α-KG-dependent dioxygenases involved in DNA and histone demethylation. The resulted hypermethylation status affects gene expression and cellular differentiation, thus promoting tumor formation.

• #15 Understanding the Role of IDH Mutation in Chondrosarcoma – University of Miami

  https://scholarship.miami.edu/esploro/outputs/doctoral/Understanding-the-Role-of-IDH-Mutation/991031447192702976

  This study provided the first evidence that IDH mutation is associated with chondrosarcoma tumorigenesis, but its mechanistic function in this malignancy is still not clearly defined. […] We found IDH1mut knockout significantly suppressed the tumorigenic properties of chondrosarcoma cells and resulted in marked attenuation of chondrosarcoma formation and elimination of the oncometabolite, D-2HG production. Our findings suggest that IDH1 mutation promotes chondrosarcoma growth through modulation of integrin, rendering the integrin molecules appealing candidates for combinatorial regimens with IDH1mut inhibitors for chondrosarcomas that harbor this mutation.

• #16 Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature

  https://www.mdpi.com/1467-3045/46/11/751

  The immune microenvironment in chondrosarcomas also plays a crucial role in tumor progression, with tumor-associated macrophages (TAMs) representing the predominant immune cell type. […] Recent studies have highlighted markers like CSF1R in TAMs as potential targets for immunomodulation. […] In chondrosarcomas (ChSs), mutations in the TP53 gene are observed in approximately 22% of cases, particularly in higher-grade tumors, such as grade 2/3 and dedifferentiated chondrosarcomas. […] Gene aberrations are common in chondrosarcomas (ChSs), with higher grades showing more abnormalities. […] The pRb pathway, disrupted in many cases of high-grade ChS, involves loss of RB1 gene heterozygosity, reduced CDKN2A/p16 expression, or increased CDK4 or cyclin D1 expression. […] The Hedgehog (HH) pathway is essential for embryogenesis and adult tissue maintenance.

• #16 Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature

  https://www.mdpi.com/1467-3045/46/11/751

  The chondrosarcoma, a cartilage-forming bone tumor, presents significant clinical challenges due to its resistance to chemotherapy and radiotherapy. […] This review explores the genetic alterations and molecular pathways involved in chondrosarcoma pathogenesis. […] While these advancements offer hope for more personalized and targeted therapeutic strategies, further clinical validation of these biomarkers is essential to improve prognostic accuracy and patient outcomes in chondrosarcoma management. […] The tumor microenvironment (TME) in chondrosarcomas is characterized by a dense and heterogeneous extracellular matrix (ECM) that supports tumor growth and metastasis through various signaling pathways. […] Hypoxia, common in the chondrosarcoma TME, activates hypoxia-inducible factors (HIF-1α and HIF-2α), which further promote metastasis by triggering pathways involved in cancer cell dormancy, angiogenesis, and ECM remodeling, as well as contributing to chemoresistance through cancer stem cell survival.

• #17 Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature

  https://www.mdpi.com/1467-3045/46/11/751

  Given its role in chondrogenesis, targeting HH signaling in chondrosarcomas (CSs) has been explored. […] The dual PI3K/mTOR inhibitor BEZ235 induced G1 arrest in CS cell lines without causing apoptosis. […] Despite limited advances in chondrosarcoma treatment, recent research has identified promising molecular targets for therapy. […] Targeting the mTOR pathway with inhibitors like rapamycin and everolimus further reduces tumor metabolism and progression, underscoring their potential to enhance chondrosarcoma treatment outcomes. […] In conclusion, identifying genetic alterations and molecular mechanisms underlying chondrosarcomas has paved the way for developing targeted therapies and prognostic biomarkers.

• #18 Mice with Trp53 and Rb1 deficiency in chondrocytes spontaneously develop chondrosarcoma via overactivation of YAP signaling | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04916-4

  Chondrosarcoma (CHS) is a rare type of soft sarcoma with increased production of cartilage matrix arising from soft bone tissues. […] Here, we generated a new transgenic chondrosarcoma model by double conditional deletions of Trp53 and Rb1 in chondrocyte lineage which spontaneously caused spinal chondrosarcoma and lung metastasis. […] Mechanistically, we found that YAP expression and activity were significantly increased in mouse Col2-Cre;Trp53f/f/Rb1f/f chondrosarcoma tissues compared to the adjacent normal cartilage. […] Knockdown of YAP in primary chondrosarcoma cells significantly inhibited chondrosarcoma proliferation, invasion, and tumorsphere formation. […] Chondrocyte lineage ablation of YAP delayed chondrosarcoma progression and lung metastasis in Col2-Cre;Trp53f/f/Rb1f/f mice.

• #19 A single-cell atlas of conventional central chondrosarcoma reveals the role of endoplasmic reticulum stress in malignant transformation | Communications Biology

  https://www.nature.com/articles/s42003-024-05790-w

  The transformation of benign lesions to malignant tumours is a crucial aspect of understanding chondrosarcomas, which are malignant cartilage tumours that could develop from benign chondroid lesions. […] To address this issue, we conducted a study analysing 11 primary cartilage tumours and controls using single-cell RNA sequencing. By creating a single-cell atlas, we were able to identify the role of endoplasmic reticulum (ER) stress in the malignant transformation of conventional central chondrosarcomas (CCCS). Our research revealed that lower levels of ER stress promote chondrosarcoma growth in a patient-derived xenograft mouse model, while intensive ER stress reduces primary chondrosarcoma cell viability. Furthermore, we discovered that the NF-B pathway alleviates ER stress-induced apoptosis during chondrosarcoma progression.

• #20 A single-cell atlas of conventional central chondrosarcoma reveals the role of endoplasmic reticulum stress in malignant transformation | Communications Biology

  https://www.nature.com/articles/s42003-024-05790-w

  Notably, the Chon2 cluster markers were enriched in response to ER stress (e.g., DDIT3, HSPA5, and TRIB3), while gene markers of the Chon1 cluster were enriched for chondrocyte differentiation. […] Therefore, we propose that cellular response to ER stress is a molecular signature associated with the malignant transformation of differentiated tumours. […] Overall, these results indicated that ER stress and NF-B signalling pathways played a critical role during the malignant transformation of chondrosarcoma. […] The present study identified ER stress as a marker for malignant transformation and we propose a prognostic model for chondroid neoplasm to aid clinical decision making and which may inform the development of new treatment strategies for CCCS by targeting the ER stress pathway.

• #21 Hypoxia-regulated exosomes mediate M2 macrophage polarization and promote metastasis in chondrosarcoma | Aging

  https://www.aging-us.com/article/205230

  Chondrosarcoma is a primary malignant bone tumor. Traditional therapy is not very effective, and it is prone to metastasis in the late stage. The tumor microenvironment (TME) plays a key role in the progression and metastasis of chondrosarcoma, and hypoxia is one of the key factors in the formation of TME. However, the detailed mechanism of how hypoxia affects tumor progression and metastasis in chondrosarcoma is still not fully understood. […] Our results suggest that hypoxia enhances the release of exosomes from chondrosarcoma cells. These hypoxia-induced exosomes promoted macrophage polarization towards the M2 phenotype, characterized by the expression of CD163 and CD206, but not the M1 phenotype, characterized by CD86 expression. […] These results suggest that chondrosarcoma cells secrete more exosomes in a hypoxic microenvironment, and these hypoxia-derived exosomes induce the polarization of macrophages into an M2 phenotype, ultimately promoting the metastatic behavior of chondrosarcoma cells.

• #22

  https://journals.lww.com/cancerjournal/fulltext/2024/20020/new_advances_in_the_treatment_of_chondrosarcoma.3.aspx

  Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. […] Resistance to chemotherapy and radiotherapy is a common dilemma for patients with chondrosarcoma, given that chondrosarcoma tumors are known to be resistant to chemotherapy and radiotherapy, thereby making these standard treatment modalities ineffective for treating this disease. […] The PD-1/PD-L1 pathway plays a significant role in immune evasion given that their interaction downregulates the T-cell-mediated response. […] The immune system normally surveils malignant cells, recognizing and removing them to prevent tumor growth. The PD-1/PD-L1 axis, an extensively studied negative regulatory immune checkpoint pathway, plays a crucial role in this process.

• #23

  https://journals.lww.com/cancerjournal/fulltext/2024/20020/new_advances_in_the_treatment_of_chondrosarcoma.3.aspx

  Tumor cells augment PD-L1 expression, which interacts with PD-1 receptors on immune cells, primarily T cells. This triggers inhibitory signals within immune cells, which dampen the antitumor response, activate a signaling cascade within T cells, and activate SHP-2, which inhibits critical T-cell activation and effector pathways. […] Therefore, targeting the PD-1/PD-L1 pathway with immune checkpoint inhibitors greatly increases the potential for cancer immunotherapy, given that blockade of PD-1/PD-L1 interactions through these inhibitors ultimately restores T-cell activity and enhances antitumor immune response and tumor regression.

• #24 Chondrosarcoma | Bone Cancer Research Trust

  https://www.bcrt.org.uk/information/information-by-type/chondrosarcoma/

  Chemotherapy and radiotherapy target rapidly dividing cells. The majority of chondrosarcomas are low grade (grade 1) and are therefore relatively slow-growing; this makes them resistant to chemotherapy and radiotherapy. […] In addition, some chondrosarcomas express a gene called 'P Glycoprotein,’ which is normally found in intestinal tissues, and in the brain. P Glycoprotein exists in healthy tissue to pump poisons out of cells. If P glycoprotein gets switched on in cancer cells it pumps chemotherapy drugs out of the tumour, rendering the drugs ineffective. […] Chondrosarcomas also tend to have a very poor blood supply meaning that it is difficult for drugs to reach the tumour cells. […] Radiotherapy resistance (radioresistance) in chondrosarcoma is caused by the loss of certain genes that are the targets of radiation.

• #25 Chondrosarcoma | Bone Cancer Research Trust

  https://www.bcrt.org.uk/information/information-by-type/chondrosarcoma/

  Loss of particular genes known as tumour suppressor genes has been shown to make cancer cells radioresistant. For example the loss of the tumour suppressor gene called P16. In around half of high grade chondrosarcomas, there is damage to P16. […] All these research findings can suggest targets for novel and specific treatments against chondrosarcoma.

• #26 Annals of Clinical & Laboratory Science

  https://www.annclinlabsci.org/content/33/2/131.full

  Molecular profiling of mesenchymal chondrosarcoma using a proteomic approach characterized the mesenchymal chondroblasts as possessing pathways that incorporate PKC- and PDGFR- signaling and anti-apoptotic bc1-2 expression. […] These observations suggest mechanisms to explain tumoral growth while protecting against apoptosis. By using a proteomic approach that enables the detection, visual quantification, cellular compartmentalization, assessment of the state of activation, and functional grouping of proteins, one can construct proliferation pathways in malignant mesenchymal chondroblasts that center around PKC- and PDGFR- signal transduction. […] Molecular commonalities between mesenchymal chondrosarcoma and non-neoplastic chondrogenesis of mesenchymal cells have been revealed by the findings of this study and by computer-assisted mining of the published data. These include expression and activation of PKC-and p38MAPK.

• #27 Annals of Clinical & Laboratory Science

  http://www.annclinlabsci.org/content/33/2/131.full?ck=nck

  Molecular profiling of mesenchymal chondrosarcoma using a proteomic approach characterized the mesenchymal chondroblasts as possessing pathways that incorporate PKC- and PDGFR- signaling and anti-apoptotic bc1-2 expression. […] The malignant mesenchymal chondroblasts show stronger expression of CD99, IL-1, cPKC-, p-PKC-/II, PDGFR-, p-JNK, Ki-67, and bc1-2 antigens. These observations suggest mechanisms to explain tumoral growth while protecting against apoptosis. […] By using a proteomic approach that enables the detection, visual quantification, cellular compartmentalization, assessment of the state of activation, and functional grouping of proteins, one can construct proliferation pathways in malignant mesenchymal chondroblasts that center around PKC- and PDGFR- signal transduction. […] Expression of CD99 appears relevant in this context, given its documented role as a mediator of MAPK (JNK and ERK) activation via a PKC pathway.

• #28 Bone: Dedifferentiated chondrosarcoma

  https://atlasgeneticsoncology.org/solid-tumor/5337/bone-dedifferentiated-chondrosarcoma

  Dedifferentiated chondrosarcoma was first proposed in 1971 by Dahlin and Beabout. It is characterized by two distinct histopathological components; a well-differentiated benign chondral lesion or chondrosarcoma (any grade) sharply juxtaposed with a high-grade non-cartilaginous component; typically there is an abrupt transition between the two tissue types. […] Pathogenesis unclear. Dahlin and Beabout suggested that dedifferentiation is the result of direct transformation of a well-differentiated cartilage lesion, while others suggested that it is related to transformation within the dense fibrotic reaction surrounding necrotic areas at the margin of the chondral component by a process analogous to the development of fibrosarcomas in bone infarcts and chronic osteomyelitis. […] Others advocate that dedifferentiation is the result of two differing clones of cells, one of which differentiates into a low-grade chondrosarcoma, while the other fails to differentiate and displays features of a high-grade sarcoma.

• #29

  https://link.springer.com/article/10.4103/0019-5413.132506

  Dedifferentiated chondrosarcomas are cartilaginous tumors that consist of two distinguishable components, a lowgrade chondrosarcoma (chondrogenic) component and a highgrade dedifferentiated (anaplastic) component. […] The underlying mechanism of dedifferentiation is unknown, but cell cycle regulators p16, p53 and retinoblastoma appear to have important roles in tumor development and dedifferentiation. […] In this article, molecular pathogenesis of dedifferentiated chondrosarcomas is reviewed. […] Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma. […] Rb-loss is associated with high malignancy in chondrosarcoma.

• #30 Bone: Dedifferentiated chondrosarcoma

  https://atlasgeneticsoncology.org/solid-tumor/5337/bone-dedifferentiated-chondrosarcoma

  Controversy remains as to whether the anaplastic and cartilaginous components are derived from a common precursor cell, or whether they represent separate genotypic lineages (collision tumour). Molecular, genetic and epigenetic studies show that both tumor components share some genetic alterations; two clones derive from a single precursor but a substantial number of genetic alterations occur after the diversion of the two components, indicating that these two clones are separated in the early phases of the disease progress and further alterations are responsible for the switch to a high-grade anaplastic sarcoma. […] Tumor suppressor gene mutations may play a major role in the development, progression, and /or differentiation of tumors. P53 gene: Mutations of p53 occur frequently in the oncogenesis of various mesenchymal neoplasms. Some authors reported that p53 overexpression was consistently present in dedifferentiated components with accompanied increased proliferative activity and an absence in low-grade cartilaginous component.

• #31

  https://www.ijcasereportsandimages.com/archive/2017/005-2017-ijcri/CR-10789-05-2017-kumar/ijcri-107895201789-kumar-full-text.php

  Mesenchymal chondrosarcoma is an uncommon, slow growing malignant tumor which is a rare variant of chondrosarcoma, having a predilection for the maxillofacial skeleton; less often involves the soft tissue sites in head and neck. […] The tumor is unique due to high tendency for late recurrence and delayed metastasis to lung, bone, and lymph nodes. […] Mesenchymal chondrosarcomas may develop from pluripotent mesenchymal stem cells and can differentiate into angioblastic, fibroblastic or cartilaginous structures, but precise pathogenesis and biological behavior is not fully understood in head and neck mesenchymal chondrosarcoma. […] Recent studies have shown the identification of new gene HEY1-NCOA2 fusion which appears to be diagnostic, but missing in other subtype of chondrosarcoma. […] Histopathologically, mesenchymal chondrosarcoma shows characteristic biphasic pattern.

• #32

  https://www.ijcasereportsandimages.com/archive/2017/005-2017-ijcri/CR-10789-05-2017-kumar/ijcri-107895201789-kumar-full-text.php

  The characteristic expression of type II collagen in matrix of mesenchymal chondrosarcoma helps in differentiation from other small cell sarcomas. […] Wide surgical excision is the mainstay treatment for chondrosarcoma in the jaw bones. […] The prognosis of the chondrosarcoma of the jaws is poor as compared to that of long bones. […] Mesenchymal chondrosarcoma shows varied clinical and radiographic features, with occurrence of this lesion in unusual locations like posterior region of jaw which shows ill-defined feature and ossification which may lead to error in clinical and histopathological diagnosis and delay in early treatment.

• #33 Intracranial Mesenchymal Chondrosarcoma | American Journal of Neuroradiology

  https://www.ajnr.org/ajnr-case-collections-diagnosis/intracranial-mesenchymal-chondrosarcoma

  The pathogenesis of this entity is unclear and various cell origins, such as embryonic cartilaginous remnants in meninges, dural fibroblasts, and meningeal multipotent mesenchymal cells, have been proposed.

• #34 Mesenchymal Chondrosarcoma – SFA

  https://curesarcoma.org/sarcoma-subtypes/mesenchymal-chondrosarcoma/

  A highly specific recurrent gene fusion between HEY1 and NCOA2 occurs in almost all mesenchymal chondrosarcomas. […] Mesenchymal chondrosarcomas are thought to arise from early, immature cartilage cells (chondroblasts), which differentiate into well-differentiated hyaline cartilage and then often undergo endochondral ossification to bone. […] The cartilage-to-bone production in this region involves the WNT/β-catenin pathway.

• #35 Google Scholar

  https://scholar.google.com/scholar_lookup?title=Studies%20on%20the%20molecular%20pathogenesis%20of%20extraskeletal%20myxoid%20chondrosarcoma-cytogenetic,%20molecular%20genetics,%20and%20cDNA%20microarray%20analyses&author=Sj%C3%B6gren&publication_year=

  Extraskeletal myxoid chondrosarcomas (EMCs) are characterized by recurrent chromosome translocations resulting in fusions of the nuclear receptor TEC to various NH2-terminal partners. […] Using spectral karyotyping and fluorescence in situ hybridization, clonal chromosome abnormalities were detected in all but one tumor. […] A t(9;22)(q22;q12) translocation was found in three cases; a del(22)(q1213) in one case; and variant translocations, including t(9;17)(q22;q1112), t(7;9;17)(q32;q22;q11), and t(9;15)(q22;q21), were detected in one case each. […] Recurrent, secondary abnormalities, including trisomy 1q, 7, 8, 12, and 19, were found in seven tumors. […] All tumors contained translocation-generated or cryptic gene fusions, including EWS-TEC (five cases, of which one was a novel fusion), TAF2N-TEC (four cases), and TCF12-TEC (one case).

• #36 Google Scholar

  https://scholar.google.com/scholar_lookup?title=Studies%20on%20the%20molecular%20pathogenesis%20of%20extraskeletal%20myxoid%20chondrosarcoma-cytogenetic,%20molecular%20genetics,%20and%20cDNA%20microarray%20analyses&author=Sj%C3%B6gren&publication_year=

  The most differentially expressed gene in both tumors was CHI3L1, which encodes a secreted glycoprotein (YKL-40) previously implicated in various pathological conditions of extracellular matrix degradation as well as in cancer. […] Our findings suggest that EMC exhibits a tumor-specific gene expression profile, including overexpression of several cancer-related genes as well as genes implicated in chondrogenesis and neural-neuroendocrine differentiation, thus distinguishing it from other soft tissue sarcomas.

• #37 Mice with Trp53 and Rb1 deficiency in chondrocytes spontaneously develop chondrosarcoma via overactivation of YAP signaling | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04916-4

  Our data showed that double deletions of Trp53 and Rb1 in chondrocytes led to the spontaneous development of chondrosarcoma through activation of YAP signaling. […] Thus, this study provides a new transgenic chondrosarcoma model and a proof of principle that the inhibition of YAP activity may be a potential therapeutic target for chondrosarcoma. […] YAP signaling acts as a potent driver of the onset and progression of chondrosarcoma. […] Our findings suggested that Hippo-YAP signaling may be a potent driver of the onset and progression of chondrosarcoma. […] Collectively, our findings suggested that metformin inhibits chondrosarcoma progression through YAP signaling.

• #38 Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression An | OTT

  https://www.dovepress.com/roles-of-eaat1-dhfr-and-fetuin-a-in-the-pathogenesis-progression-and-p-peer-reviewed-fulltext-article-OTT

  Aims: Chondrosarcoma (CS) is a high-morbidity, relatively common bone malignancy without well-established biomarkers. The proteins EAAT1, DHFR, and fetuin-A have been investigated in many cancers, but their specific relationship to CS has not been reported. The present study examined EAAT1, DHFR, and fetuin-A expression in CS and the clinicopathological significance of these proteins in CS pathogenesis, progression, and prognosis. […] Conclusion: EAAT1, DHFR, and fetuin-A may be important biomarkers of the pathogenesis and progression of CS and predictors of its prognosis. […] In the present study, EAAT1, DHFR, and fetuin-A expression levels revealed by immunohistochemistry were found to be higher in CS tumors than in chondromas, indicating that these proteins might play an important role in the pathogenesis of CS.

• #39 Roles Of EAAT1, DHFR, And Fetuin-A In The Pathogenesis, Progression An | OTT

  https://www.dovepress.com/roles-of-eaat1-dhfr-and-fetuin-a-in-the-pathogenesis-progression-and-p-peer-reviewed-fulltext-article-OTT

  These findings suggest that EAAT1, DHFR, and fetuin-A may be useful biomarkers for this malignancy. […] Notably, our finding showing that EAAT1 expression was significantly higher in CS tissues with invasion than in those without suggests that EAAT1 may serve as a specific marker of invasive CS. […] Together these results indicate that EAAT1, DHFR, and fetuin-A proteins may serve as biomarkers of pathogenesis and progression, and predictors of prognosis, in CS.

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