Materiały źródłowe

• #1 Chordoma: a case series and review of the literature | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-018-1784-y

  Chordoma is a rare malignant tumor of the skull base and axial skeleton, with an incidence of less than 0.1/100,000 per year. […] The pathogenesis of chordoma remains undetermined. It is presumed that the notochord developed in fetal development evolved from cellular residues. […] Chordoma is a primary bone tumor originating from a non-differentiated notochordal residue and developed in the vertebrae; it is most frequently seen in sacral (50%), skull base (30%) and mobile spine (20%). […] The pathogenesis of chordoma is unclear but tumor cells are characterized by a notochordal differentiation. […] Cytotoxic chemotherapy does not have any proven benefit and therefore it is not recommended. […] Tamborini et al. showed that beta-type platelet-derived growth factor receptor (PDGFRB) was highly expressed and phosphorylated, but platelet-derived growth factor receptor alpha (PDGFRA) and KIT were less expressed in chordomas.

• #2 Chordoma – Wikipedia

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

  Chordoma is a rare slow-growing neoplasm (cancer) that arises from cellular remnants of the notochord in the bones of the skull base and spine. […] The evidence for the notochordal origin of chordoma is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, expression of brachyury, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life. […] A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma. […] There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families. […] While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma.

• #3 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #4 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #5 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Chordoma is a rare bone cancer of unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. […] Chordomas are thought to arise from primitive notochordal remnants along the axial skeleton. During development, the notochord is surrounded by the developing vertebral column. In adults, remnants of the notochord are present as the nucleus pulposus of the intervertebral discs. Notochordal remnants that are extradural are most common in the sacrococcygeal region but can be found at any site along the length of the axial skeleton. The distribution of tumors matches the distribution of notochordal remnants.

• #6 What is chordoma spinal cancer? | Chordoma UK

  https://chordoma-uk.org/what-is-chordoma-spinal-cancer

  Chordoma is thought to arise from embryonic tissue (notochordal cells), which normally disappears before birth, but can persist in about 20% of the population after birth. […] The reason why a person develops chordoma is unknown. In a small number of individuals with chordoma it runs in families but this is very rare.

• #7 Chordoma – Wikipedia

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

  Chordoma is a rare slow-growing neoplasm (cancer) that arises from cellular remnants of the notochord in the bones of the skull base and spine. […] The evidence for the notochordal origin of chordoma is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, expression of brachyury, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life. […] A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma. […] There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families. […] While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma.

• #8 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #9 Chordoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chordoma/

  Changes in the TBXT gene have been associated with chordoma. An inherited duplication of the TBXT gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family. […] The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the TBXT gene, and the cause of the disorder in these individuals is unknown.

• #10 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #11 What You Need to Know About Chordoma Cancer

  https://www.healthline.com/health/cancer/chordoma-cancer

  Chordoma tumors form from notochordal cells remnants of the notochord, a structure in an embryo thats replaced by the spine during the first trimester of development. […] The exact reason why malignancies form in notochordal cells isnt known or understood. […] Around 95% of people with chordoma cancer have an SNP (snip) variation in the DNA sequence of their brachyury gene. This SNP variation doesnt cause chordoma but increases the risk of developing it. […] There are a few instances of families who have several members with chordoma. This rare occurrence appears to be associated with having an extra copy of the brachyury gene. […] Children born with the rare genetic condition tuberous sclerosis complex (TSC) are at a higher risk for developing chordoma cancer than most people without this condition. Its thought that changes to the genes responsible for TSC may also heighten someones risk for chordoma cancer. […] More research is needed on the hereditary and genetic causes of chordoma. There arent any lifestyle factors that cause this condition or increase the risk for it.

• #12 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #13 Chordoma: Symptoms, causes, treatment, and more

  https://www.medicalnewstoday.com/articles/chordoma

  Chordoma may result from genetic changes. About 80% of individuals with chordoma have a genetic variation in a gene responsible for spinal development. […] However, many people in the general population also have this variant. And most individuals with this variant do not go on to develop chordoma. Ongoing studies may shed more light on why some people develop chordoma, and others do not.

• #14 Chordoma – Wikipedia

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

  Chordoma is a rare slow-growing neoplasm (cancer) that arises from cellular remnants of the notochord in the bones of the skull base and spine. […] The evidence for the notochordal origin of chordoma is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, expression of brachyury, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life. […] A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma. […] There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families. […] While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma.

• #15 Chordoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chordoma/

  Changes in the TBXT gene have been associated with chordoma. An inherited duplication of the TBXT gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family. […] The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the TBXT gene, and the cause of the disorder in these individuals is unknown.

• #16 Chordoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chordoma/

  Changes in the TBXT gene have been associated with chordoma. An inherited duplication of the TBXT gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family. […] The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the TBXT gene, and the cause of the disorder in these individuals is unknown.

• #17 Chordoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chordoma/

  Changes in the TBXT gene have been associated with chordoma. An inherited duplication of the TBXT gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family. […] The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the TBXT gene, and the cause of the disorder in these individuals is unknown.

• #18 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #19 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. […] A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes, including whole or partial losses of chromosomes 3, 4, 10, and 13; gains in chromosome 7; and rearrangements of chromosome 1p. All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

• #20 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #21 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. […] A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes, including whole or partial losses of chromosomes 3, 4, 10, and 13; gains in chromosome 7; and rearrangements of chromosome 1p. All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

• #22 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #23 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. […] A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes, including whole or partial losses of chromosomes 3, 4, 10, and 13; gains in chromosome 7; and rearrangements of chromosome 1p. All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

• #24 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #25 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. […] A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes, including whole or partial losses of chromosomes 3, 4, 10, and 13; gains in chromosome 7; and rearrangements of chromosome 1p. All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

• #26 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Genomic study uncovers germline ARID1B and mitochondrial variants potentially driving pediatric chordoma genesis. […] Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children, says Katrina OHalloran, MD, MS, pediatric neuro-oncologist and first author of the study. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the diseasepoorly differentiated pediatric chordomais the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell. […] The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers.

• #27 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240530/Researchers-uncover-two-classes-of-genetic-causes-for-pediatric-chordoma.aspx

  Little is known about the genetics and biology of chordoma, a rare and aggressive bone tumor. A team of researchers led by Xiaowu Gai, PhD and Jaclyn Biegel, PhD, FACMG, at the Center for Personalized Medicine at Children’s Hospital Los Angeles, has recently published a genomic study that uncovered two classes of genetic causes for chordoma in children by conducting some genomic detective work. Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the disease, poorly differentiated pediatric chordoma, is the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell.

• #28 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Tumors from five of the 23 pediatric chordoma patients (22%) were shown to carry short inframe insertions and deletions (indels) in the ARID1B gene. […] A significant fraction of the adult chordoma patients (5%) carried comparable inherited ARID1B indels. […] These findings implicate a common disease pathway in different subtypes of chordoma that may alter gene expression through defects in the SWI/SNF chromatin remodeling complex, says Dr. Jaclyn Biegel, Director of the Center for Personalized Medicine and a senior author of the study. […] This study implicates a potential interplay of chromatin remodeling and mitochondrial metabolism in chordoma genesis, says Dr. Gai, Director of Bioinformatics, Center for Personalized Medicine, and senior study author.

• #29 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240530/Researchers-uncover-two-classes-of-genetic-causes-for-pediatric-chordoma.aspx

  The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers. […] Tumors from five of the 23 pediatric chordoma patients (22%) were shown to carry short inframe insertions and deletions (indels) in the ARID1B gene. […] A significant fraction of the adult chordoma patients (5%) carried comparable inherited ARID1B indels. […] „These findings implicate a common disease pathway in different subtypes of chordoma that may alter gene expression through defects in the SWI/SNF chromatin remodeling complex,” says Dr. Jaclyn Biegel, Director of the Center for Personalized Medicine and a senior author of the study. […] „This study implicates a potential interplay of chromatin remodeling and mitochondrial metabolism in chordoma genesis,” says Dr. Gai, Director of Bioinformatics, Center for Personalized Medicine, and senior study author.

• #30 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Genomic study uncovers germline ARID1B and mitochondrial variants potentially driving pediatric chordoma genesis. […] Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children, says Katrina OHalloran, MD, MS, pediatric neuro-oncologist and first author of the study. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the diseasepoorly differentiated pediatric chordomais the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell. […] The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers.

• #31 Potential Causes of Rare and Lethal Bone Cancer Identified | Technology Networks

  https://www.technologynetworks.com/cancer-research/news/potential-causes-of-rare-and-lethal-bone-cancer-identified-387334

  Little is known about the genetics and biology of chordoma, a rare and aggressive bone tumor. […] A team of researchers led by Xiaowu Gai, PhD, and Jaclyn Biegel, PhD, FACMG, at the Center for Personalized Medicine at Childrens Hospital Los Angeles, has recently published a genomic study that uncovered two classes of genetic causes for chordoma in children by conducting some genomic detective work. […] For example, pediatric solid tumors are more likely to be driven by underlying germline changesalterations that can be passed on to future generationsthat increase the risk for cancer. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the diseasepoorly differentiated pediatric chordomais the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell.

• #32 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. […] A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes, including whole or partial losses of chromosomes 3, 4, 10, and 13; gains in chromosome 7; and rearrangements of chromosome 1p. All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

• #33 Chordoma: Practice Essentials, History of the Disease, Epidemiology

  https://emedicine.medscape.com/article/250902-overview

  Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. […] A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes, including whole or partial losses of chromosomes 3, 4, 10, and 13; gains in chromosome 7; and rearrangements of chromosome 1p. All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

• #34 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #35 Chordoma – Wikipedia

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

  Chordoma is a rare slow-growing neoplasm (cancer) that arises from cellular remnants of the notochord in the bones of the skull base and spine. […] The evidence for the notochordal origin of chordoma is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, expression of brachyury, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life. […] A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma. […] There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families. […] While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma.

• #36 Chordoma – Wikipedia

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

  Chordoma is a rare slow-growing neoplasm (cancer) that arises from cellular remnants of the notochord in the bones of the skull base and spine. […] The evidence for the notochordal origin of chordoma is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, expression of brachyury, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life. […] A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma. […] There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families. […] While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma.

• #37 Chordoma – Wikipedia

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

  Chordoma is a rare slow-growing neoplasm (cancer) that arises from cellular remnants of the notochord in the bones of the skull base and spine. […] The evidence for the notochordal origin of chordoma is the location of the tumors (along the neuraxis), the similar immunohistochemical staining patterns, expression of brachyury, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life. […] A small number of families have been reported in which multiple relatives have been affected by chordoma. In four of these families, duplication of the brachyury gene was found to be responsible for causing chordoma. […] There are currently no known environmental risk factors for chordoma. As noted above germline duplication of brachyury has been identified as a major susceptibility mechanism in several chordoma families. […] While most people with chordoma have no other family members with the disease, rare occurrences of multiple cases within families have been documented. This suggests that some people may be genetically predisposed to develop chordoma.

• #38 Chordoma | About the Disease | GARD

  https://rarediseases.info.nih.gov/diseases/1303/chordoma

  Genetic mutations can be hereditary, when parents pass them down to their children, or they may occur randomly when cells are dividing. […] Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these. […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.

• #39 Chordoma | About the Disease | GARD

  https://rarediseases.info.nih.gov/diseases/1303/chordoma

  Genetic mutations can be hereditary, when parents pass them down to their children, or they may occur randomly when cells are dividing. […] Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these. […] Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. […] Based on GARD’s current data, this disease can be inherited in the following pattern(s): Autosomal Dominant. […] Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.

• #40 Chordoma: What It Is, Types, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17916-chordoma

  Chordoma is a rare malignant (cancerous) bone tumor that forms in your spine or the base of your skull. […] Researchers dont know exactly why chordomas form. But they think changes (mutations) in the TBXT gene are likely involved. […] A chordoma develops from cells of the notochord. This is a structure thats present in a developing embryo and is important for the future development of its spine. […] A change in the TBXT gene may trigger the growth of these cells, leading to a chordoma. […] People with a genetic condition called tuberous sclerosis are at higher risk of developing chordoma.

• #41 Chordoma Causes | Expert Surgeon | Aaron Cohen-Gadol, MD | Aaron Cohen-Gadol, MD

  https://www.aaroncohen-gadol.com/en/patients/chordoma/types/causes

  Other potential factors that may increase the risk of developing a chordoma include excessive exposure to ionizing radiation, or exposure to chemicals like vinyl chloride, though this link has not been well established. Most cases of chordoma occur in people without any known risk factors, and the exact cause of chordoma is not yet known. […] Although the risk factors for chordoma are not well understood, studies have suggested that people with certain genetic conditions, such as tuberous sclerosis, may have an increased risk of developing a chordoma. […] Chordoma doesnt usually run in families. However, there have been a few reported cases of families with multiple members affected by chordoma, which suggests that there might be a genetic component to the development of this cancer. […] Chordoma has also been reported in other genetic conditions, such as tuberous sclerosis. The link between chordoma, a nearly one-in-a-million cancer, and a rare genetic disorder is not well established due to the scarcity of reports. […] Most cases of chordoma occur in people without any known risk factors, and the exact cause of chordoma is not yet known.

• #42 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #43 Chordoma | Bone Cancer Research Trust

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

  Inheriting an extra copy of the brachyury gene is thought to be responsible for the familial form of chordoma in most cases. […] 70% of TSC syndrome cases are diagnosed during childhood, and many reports link the mutation of genes TSC1 and TSC2 to the development of childhood chordomas (9). […] Changes to the way the genetic code is expressed, without alteration of the DNA code sequence, are known as epigenetic modifications. In cancer cells, these changes can lead to the activation of tumour promoting genes (oncogenes) and the silencing of tumour suppressor genes. […] The three main epigenetic mechanism include DNA methylation, histone modifications post-transcriptional gene regulation by non-coding RNA (miRNA). All three are found in chordoma and they lead to tumour cell growth and proliferation (29).

• #44 Chordoma | Bone Cancer Research Trust

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

  Inheriting an extra copy of the brachyury gene is thought to be responsible for the familial form of chordoma in most cases. […] 70% of TSC syndrome cases are diagnosed during childhood, and many reports link the mutation of genes TSC1 and TSC2 to the development of childhood chordomas (9). […] Changes to the way the genetic code is expressed, without alteration of the DNA code sequence, are known as epigenetic modifications. In cancer cells, these changes can lead to the activation of tumour promoting genes (oncogenes) and the silencing of tumour suppressor genes. […] The three main epigenetic mechanism include DNA methylation, histone modifications post-transcriptional gene regulation by non-coding RNA (miRNA). All three are found in chordoma and they lead to tumour cell growth and proliferation (29).

• #45 Chordoma Causes | Expert Surgeon | Aaron Cohen-Gadol, MD | Aaron Cohen-Gadol, MD

  https://www.aaroncohen-gadol.com/en/patients/chordoma/types/causes

  Other potential factors that may increase the risk of developing a chordoma include excessive exposure to ionizing radiation, or exposure to chemicals like vinyl chloride, though this link has not been well established. Most cases of chordoma occur in people without any known risk factors, and the exact cause of chordoma is not yet known. […] Although the risk factors for chordoma are not well understood, studies have suggested that people with certain genetic conditions, such as tuberous sclerosis, may have an increased risk of developing a chordoma. […] Chordoma doesnt usually run in families. However, there have been a few reported cases of families with multiple members affected by chordoma, which suggests that there might be a genetic component to the development of this cancer. […] Chordoma has also been reported in other genetic conditions, such as tuberous sclerosis. The link between chordoma, a nearly one-in-a-million cancer, and a rare genetic disorder is not well established due to the scarcity of reports. […] Most cases of chordoma occur in people without any known risk factors, and the exact cause of chordoma is not yet known.

• #46 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Chordoma.aspx

  Research is still ongoing to understand the underlying mechanism behind the development of chordoma. According to some reports, a protein called brachyury is overexpressed in chordoma. […] Although inherited chordomas have been recorded, they are usually sporadic, and little research has looked into their hereditary occurrence. […] The molecular mechanisms that lead to chordomagenesis have yet to be thoroughly elucidated, particularly in terms of differentially expressed genes implicated in chordomagenesis. […] Chordomas have been studied using G-banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) techniques to find chromosomal aberrations. […] In chordomas, several indicators that contribute to tumor progression have been identified. […] Brachyury is a T-box transcription factor that is encoded by the T or TBXT gene and has been proven to be important in notochord development. […] Furthermore, when compared to other neoplasms, chordoma is the only one that overexpresses brachyury.

• #47 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Chordoma.aspx

  Research is still ongoing to understand the underlying mechanism behind the development of chordoma. According to some reports, a protein called brachyury is overexpressed in chordoma. […] Although inherited chordomas have been recorded, they are usually sporadic, and little research has looked into their hereditary occurrence. […] The molecular mechanisms that lead to chordomagenesis have yet to be thoroughly elucidated, particularly in terms of differentially expressed genes implicated in chordomagenesis. […] Chordomas have been studied using G-banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) techniques to find chromosomal aberrations. […] In chordomas, several indicators that contribute to tumor progression have been identified. […] Brachyury is a T-box transcription factor that is encoded by the T or TBXT gene and has been proven to be important in notochord development. […] Furthermore, when compared to other neoplasms, chordoma is the only one that overexpresses brachyury.

• #48 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Chordoma.aspx

  Research is still ongoing to understand the underlying mechanism behind the development of chordoma. According to some reports, a protein called brachyury is overexpressed in chordoma. […] Although inherited chordomas have been recorded, they are usually sporadic, and little research has looked into their hereditary occurrence. […] The molecular mechanisms that lead to chordomagenesis have yet to be thoroughly elucidated, particularly in terms of differentially expressed genes implicated in chordomagenesis. […] Chordomas have been studied using G-banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) techniques to find chromosomal aberrations. […] In chordomas, several indicators that contribute to tumor progression have been identified. […] Brachyury is a T-box transcription factor that is encoded by the T or TBXT gene and has been proven to be important in notochord development. […] Furthermore, when compared to other neoplasms, chordoma is the only one that overexpresses brachyury.

• #49 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Tumors from five of the 23 pediatric chordoma patients (22%) were shown to carry short inframe insertions and deletions (indels) in the ARID1B gene. […] A significant fraction of the adult chordoma patients (5%) carried comparable inherited ARID1B indels. […] These findings implicate a common disease pathway in different subtypes of chordoma that may alter gene expression through defects in the SWI/SNF chromatin remodeling complex, says Dr. Jaclyn Biegel, Director of the Center for Personalized Medicine and a senior author of the study. […] This study implicates a potential interplay of chromatin remodeling and mitochondrial metabolism in chordoma genesis, says Dr. Gai, Director of Bioinformatics, Center for Personalized Medicine, and senior study author.

• #50 Potential Causes of Rare and Lethal Bone Cancer Identified | Technology Networks

  https://www.technologynetworks.com/cancer-research/news/potential-causes-of-rare-and-lethal-bone-cancer-identified-387334

  The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers. […] Tumors from five of the 23 pediatric chordoma patients (22%) were shown to carry short inframe insertions and deletions (indels) in the ARID1B gene. […] A significant fraction of the adult chordoma patients (5%) carried comparable inherited ARID1B indels. […] These findings implicate a common disease pathway in different subtypes of chordoma that may alter gene expression through defects in the SWI/SNF chromatin remodeling complex, says Dr. Jaclyn Biegel, Director of the Center for Personalized Medicine and a senior author of the study. […] This study implicates a potential interplay of chromatin remodeling and mitochondrial metabolism in chordoma genesis, says Dr. Gai, Director of Bioinformatics, Center for Personalized Medicine, and senior study author.

• #51 Chordoma | Bone Cancer Research Trust

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

  Inheriting an extra copy of the brachyury gene is thought to be responsible for the familial form of chordoma in most cases. […] 70% of TSC syndrome cases are diagnosed during childhood, and many reports link the mutation of genes TSC1 and TSC2 to the development of childhood chordomas (9). […] Changes to the way the genetic code is expressed, without alteration of the DNA code sequence, are known as epigenetic modifications. In cancer cells, these changes can lead to the activation of tumour promoting genes (oncogenes) and the silencing of tumour suppressor genes. […] The three main epigenetic mechanism include DNA methylation, histone modifications post-transcriptional gene regulation by non-coding RNA (miRNA). All three are found in chordoma and they lead to tumour cell growth and proliferation (29).

• #52 Chordoma—Current Understanding and Modern Treatment Paradigms

  https://www.mdpi.com/2077-0383/10/5/1054

  The precise mechanism underlying the transformation from notochordal vestige to chordoma is not well-understood, although recent studies have highlighted several chromosomal and cell cycle aberrations thought to contribute to chordomagenesis. Overexpression of both p53 and CDK4, for instance, which function in the G1 phase of the cell cycle, has been shown to be present in some chordomas and is correlated with decreased overall survival. […] Brachyury is expressed transiently in embryonic notochord and normally silenced in post-developmental tissues but has been shown to be aberrantly re-expressed in chordoma and some evidence exists for its causative role in chordomagenesis. […] The fibroblast growth factor (FGF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway mediates expression and signaling of brachyury in chordomas and may also play a role in chordomagenesis.

• #53 Chordoma—Current Understanding and Modern Treatment Paradigms

  https://www.mdpi.com/2077-0383/10/5/1054

  Dysfunctional signaling within an RTK cascade can thus lead to the aberrant behavior observed in tumor cells and oncogenic mutations have been documented in a number of different RTK families. With chordoma in particular, platelet-derived growth factor (PDGF) receptor (PDGFR), epidermal growth factor (EGF) receptor (EGFR) and hepatocyte growth factor (HGF) receptor (c-Met) are three RTKs thought to play a role in pathogenesis and malignant potential, as each has been shown to be overexpressed in chordoma.

• #54 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #55 Chordoma Causes, Symptoms, and Treatments

  https://www.upmc.com/services/orthopaedics/conditions/chordoma

  Chordoma develops from the notochord, a cartilage-like structure formed in the first few weeks of fetal development. The spine replaces the notochord before birth. But if some notochord cells get left behind, they can turn into chordomas. […] There’s no known cause for why chordomas form in some people and not others. Chordoma doesn’t appear to be triggered by environmental or lifestyle factors. Its not caused by a pre-existing health condition or by using any medicines. […] Chordoma also doesnt seem to run in families, although there are rare cases of more than one person in a family having chordoma. […] Some people with chordoma have small changes in their genes. Researchers are using this information to try to discover how chordomas form. […] Because there’s no known cause of chordomas, risk factors are also unknown.

• #56 Chordoma | Brain Tumor Center | Stanford Medicine

  https://med.stanford.edu/brain-tumor/conditions/chordoma.html

  Chordomas arise from remnants of notochord, which precedes the spinal column during embryonic development. What causes notochord cells to become cancerous in some people is still not fully known, but researchers are actively working to find the answer. There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait. […] Chordomas have a high local recurrence rate, meaning they can come back after successful treatment usually in the same place as the first tumor. This is called a local recurrence. In selected cases, a reoperation is recommended.

• #57 Chordoma Causes, Symptoms, and Treatments

  https://www.upmc.com/services/orthopaedics/conditions/chordoma

  Chordoma develops from the notochord, a cartilage-like structure formed in the first few weeks of fetal development. The spine replaces the notochord before birth. But if some notochord cells get left behind, they can turn into chordomas. […] There’s no known cause for why chordomas form in some people and not others. Chordoma doesn’t appear to be triggered by environmental or lifestyle factors. Its not caused by a pre-existing health condition or by using any medicines. […] Chordoma also doesnt seem to run in families, although there are rare cases of more than one person in a family having chordoma. […] Some people with chordoma have small changes in their genes. Researchers are using this information to try to discover how chordomas form. […] Because there’s no known cause of chordomas, risk factors are also unknown.

• #58 Chordoma Causes | Expert Surgeon | Aaron Cohen-Gadol, MD | Aaron Cohen-Gadol, MD

  https://www.aaroncohen-gadol.com/en/patients/chordoma/types/causes

  Other potential factors that may increase the risk of developing a chordoma include excessive exposure to ionizing radiation, or exposure to chemicals like vinyl chloride, though this link has not been well established. Most cases of chordoma occur in people without any known risk factors, and the exact cause of chordoma is not yet known. […] Although the risk factors for chordoma are not well understood, studies have suggested that people with certain genetic conditions, such as tuberous sclerosis, may have an increased risk of developing a chordoma. […] Chordoma doesnt usually run in families. However, there have been a few reported cases of families with multiple members affected by chordoma, which suggests that there might be a genetic component to the development of this cancer. […] Chordoma has also been reported in other genetic conditions, such as tuberous sclerosis. The link between chordoma, a nearly one-in-a-million cancer, and a rare genetic disorder is not well established due to the scarcity of reports. […] Most cases of chordoma occur in people without any known risk factors, and the exact cause of chordoma is not yet known.

• #59 Chordoma: What is Chordoma, its Causes?

  https://www.yashodahospitals.com/diseases-treatments/chordoma-causes/

  Some of the major causes that may lead to the development of chordoma in individuals are: […] Genetic defects […] Exposure to certain chemicals for prolonged period […] Neurofibromatosis 2.

• #60 Chordoma: What is Chordoma, its Causes?

  https://www.yashodahospitals.com/diseases-treatments/chordoma-causes/

  Some of the major causes that may lead to the development of chordoma in individuals are: […] Genetic defects […] Exposure to certain chemicals for prolonged period […] Neurofibromatosis 2.

• #61 Chordoma: What It Is, Types, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17916-chordoma

  Chordoma is a rare malignant (cancerous) bone tumor that forms in your spine or the base of your skull. […] Researchers dont know exactly why chordomas form. But they think changes (mutations) in the TBXT gene are likely involved. […] A chordoma develops from cells of the notochord. This is a structure thats present in a developing embryo and is important for the future development of its spine. […] A change in the TBXT gene may trigger the growth of these cells, leading to a chordoma. […] People with a genetic condition called tuberous sclerosis are at higher risk of developing chordoma.

• #62

  https://www.orthobullets.com/pathology/8032/chordoma

  Chordomas are malignant tumors of primitive notochordal origin that most commonly occur in the sacrum and coccyx. […] forms from malignant transformation in residual notochordal cells resulting in midline location.

• #63 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #64 What You Need to Know About Chordoma Cancer

  https://www.healthline.com/health/cancer/chordoma-cancer

  Chordoma tumors form from notochordal cells remnants of the notochord, a structure in an embryo thats replaced by the spine during the first trimester of development. […] The exact reason why malignancies form in notochordal cells isnt known or understood. […] Around 95% of people with chordoma cancer have an SNP (snip) variation in the DNA sequence of their brachyury gene. This SNP variation doesnt cause chordoma but increases the risk of developing it. […] There are a few instances of families who have several members with chordoma. This rare occurrence appears to be associated with having an extra copy of the brachyury gene. […] Children born with the rare genetic condition tuberous sclerosis complex (TSC) are at a higher risk for developing chordoma cancer than most people without this condition. Its thought that changes to the genes responsible for TSC may also heighten someones risk for chordoma cancer. […] More research is needed on the hereditary and genetic causes of chordoma. There arent any lifestyle factors that cause this condition or increase the risk for it.

• #65 Genetic Clues to Chordoma Etiology: A Protocol to Identify Sporadic Chordoma Patients for Studies of Cancer-Susceptibility Genes | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT01200680/genetic-clues-to-chordoma-etiology-a-protocol-to-identify-sporadic-chordoma-patients-for-studies-of-cancer-susceptibility-genes?mp=s&id=855&slug=chordoma

  Chordoma is a rare, slow growing, often fatal bone cancer derived from remnants of the embryonic notochord. […] Reports of a small number of families worldwide with two or more relatives with chordoma support a role for susceptibility genes in chordoma etiology. […] Although most chordomas are sporadic, we previously identified germline duplication of the T gene (T-dup+), now designated TBXT, which encodes brachyury, a transcription factor that plays an important role in embryonic development, as a major susceptibility mechanism in familial chordoma. A common polymorphism in TBXT is also associated with an increased risk for both familial and sporadic chordoma. […] Thus, a better understanding of predisposing factors and molecular processes in chordoma is critically needed.

• #66 Chordoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430846/

  Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified. […] There are currently a few reported familial clusters of chordomas.

• #67 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Genomic study uncovers germline ARID1B and mitochondrial variants potentially driving pediatric chordoma genesis. […] Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children, says Katrina OHalloran, MD, MS, pediatric neuro-oncologist and first author of the study. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the diseasepoorly differentiated pediatric chordomais the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell. […] The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers.

• #68 Chordoma: What It Is, Types, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17916-chordoma

  Chordoma is a rare malignant (cancerous) bone tumor that forms in your spine or the base of your skull. […] Researchers dont know exactly why chordomas form. But they think changes (mutations) in the TBXT gene are likely involved. […] A chordoma develops from cells of the notochord. This is a structure thats present in a developing embryo and is important for the future development of its spine. […] A change in the TBXT gene may trigger the growth of these cells, leading to a chordoma. […] People with a genetic condition called tuberous sclerosis are at higher risk of developing chordoma.

• #69 Childhood Chordoma – NCI

  https://www.cancer.gov/types/bone/patient/child-chordoma-treatment-pdq

  Chordoma in children is caused by certain changes in the way cells function, especially how they grow and divide into new cells. Often, the exact cause of these cell changes is unknown. […] A risk factor is anything that increases the chance of getting a disease. Children who have an inherited condition called tuberous sclerosis may be at an increased risk of chordoma. Not every child with this risk factor will develop a chordoma. And it will develop in some children who don’t have a known risk factor. Talk with your child’s doctor if you think your child may be at risk.

• #70 Understanding chordoma | Chordoma Foundation

  https://www.chordomafoundation.org/understanding-chordoma/

  There are no known environmental, dietary, or lifestyle risk factors for chordoma. The vast majority of chordomas occur at random and not as a direct result of an inherited genetic trait; however, there are several genetic factors associated with chordoma. […] For example, more than 95 percent of individuals with chordoma have a single-letter variation, called a SNP (snip), in the DNA sequence of a gene called brachyury (also known as TBXT). This SNP causes an increase in the risk of developing chordoma, but does not by itself cause chordoma. […] It is known that some of the families with familial chordoma have an extra copy of the brachyury gene, but currently, there is no available test for the presence of extra copies of the gene. […] Changes in either of two genes involved in Tuberous Sclerosis Complex (TSC1 and TSC2) can cause a predisposition to developing chordoma.

• #71 Chordoma Causes, Symptoms, and Treatments

  https://www.upmc.com/services/orthopaedics/conditions/chordoma

  Chordoma develops from the notochord, a cartilage-like structure formed in the first few weeks of fetal development. The spine replaces the notochord before birth. But if some notochord cells get left behind, they can turn into chordomas. […] There’s no known cause for why chordomas form in some people and not others. Chordoma doesn’t appear to be triggered by environmental or lifestyle factors. Its not caused by a pre-existing health condition or by using any medicines. […] Chordoma also doesnt seem to run in families, although there are rare cases of more than one person in a family having chordoma. […] Some people with chordoma have small changes in their genes. Researchers are using this information to try to discover how chordomas form. […] Because there’s no known cause of chordomas, risk factors are also unknown.

• #72 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Genomic study uncovers germline ARID1B and mitochondrial variants potentially driving pediatric chordoma genesis. […] Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children, says Katrina OHalloran, MD, MS, pediatric neuro-oncologist and first author of the study. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the diseasepoorly differentiated pediatric chordomais the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell. […] The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers.

• #73 Team finds new potential causes of rare and lethal bone cancer

  https://medicalxpress.com/news/2024-05-team-potential-rare-lethal-bone.html

  Little is known about the genetics and biology of chordoma, a rare and aggressive bone tumor. […] A team of researchers led by Xiaowu Gai, Ph.D. and Jaclyn Biegel, Ph.D., FACMG, at the Center for Personalized Medicine at Children’s Hospital Los Angeles, has published a genomic study that uncovered two classes of genetic causes for chordoma in children by conducting some genomic detective work. […] „Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children,” says Katrina O’Halloran, MD, MS, pediatric neuro-oncologist and first author of the study. […] For example, pediatric solid tumors are more likely to be driven by underlying germline changes—alterations that can be passed on to future generations—that increase the risk for cancer.

• #74 Chordoma: A Rare Bone Cancer of the Skull Base and Spine | Pacific Neuroscience Institute

  https://www.pacificneuroscienceinstitute.org/blog/brain-tumor/chordoma-a-rare-bone-cancer-of-the-skull-base-and-spine/

  To date, no medication has been found to be the magic bullet to treat chordomas. However, there are a few promising options, especially when genetic targets are identified. Naturally, our patients chordomas are evaluated with thorough genetic sequencing to analyze gene mutations. If the patient is a candidate for targeted therapy, this can be an option for our neuro-oncologists.

• #75 Chordoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/chordoma/

  Changes in the TBXT gene have been associated with chordoma. An inherited duplication of the TBXT gene identified in a few families is associated with an increased risk of developing a chordoma. Duplications or increases in activity (expression) of the TBXT gene have also been identified in people with chordoma who have no history of the disorder in their family. […] The specific mechanism by which excess brachyury protein contributes to the development of chordomas is unclear. Some people with chordoma do not have changes in the TBXT gene, and the cause of the disorder in these individuals is unknown.

• #76 Chordoma Treatment Program | Massachusetts General Hospital

  https://www.massgeneral.org/cancer-center/treatments-and-services/sarcoma/chordoma

  Chordoma is a rare, slow-growing malignant tumor believed to arise from cellular remnants of the notochord. […] Their research is aimed at discovering the pathogenesis of chordomas and uncovering tumor markers to guide future therapies. […] Physician-scientists in the Sarcoma Molecular Biology laboratory are pursuing research to identify the genetic abnormalities associated with chordoma. […] Our goal is to search for genetic or hereditary factors that may help us to better understand the disease and suggest new therapies.

• #77 Chordoma—Current Understanding and Modern Treatment Paradigms

  https://www.mdpi.com/2077-0383/10/5/1054

  The precise mechanism underlying the transformation from notochordal vestige to chordoma is not well-understood, although recent studies have highlighted several chromosomal and cell cycle aberrations thought to contribute to chordomagenesis. Overexpression of both p53 and CDK4, for instance, which function in the G1 phase of the cell cycle, has been shown to be present in some chordomas and is correlated with decreased overall survival. […] Brachyury is expressed transiently in embryonic notochord and normally silenced in post-developmental tissues but has been shown to be aberrantly re-expressed in chordoma and some evidence exists for its causative role in chordomagenesis. […] The fibroblast growth factor (FGF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway mediates expression and signaling of brachyury in chordomas and may also play a role in chordomagenesis.

• #78 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Tumors from five of the 23 pediatric chordoma patients (22%) were shown to carry short inframe insertions and deletions (indels) in the ARID1B gene. […] A significant fraction of the adult chordoma patients (5%) carried comparable inherited ARID1B indels. […] These findings implicate a common disease pathway in different subtypes of chordoma that may alter gene expression through defects in the SWI/SNF chromatin remodeling complex, says Dr. Jaclyn Biegel, Director of the Center for Personalized Medicine and a senior author of the study. […] This study implicates a potential interplay of chromatin remodeling and mitochondrial metabolism in chordoma genesis, says Dr. Gai, Director of Bioinformatics, Center for Personalized Medicine, and senior study author.

• #79 Team finds new potential causes of rare and lethal bone cancer

  https://medicalxpress.com/news/2024-05-team-potential-rare-lethal-bone.html

  Previous chordoma studies revealed the primary genetic defect in one subtype of the disease, poorly differentiated pediatric chordoma, is the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell. […] „These findings implicate a common disease pathway in different subtypes of chordoma that may alter gene expression through defects in the SWI/SNF chromatin remodeling complex,” says Dr. Jaclyn Biegel, Director of the Center for Personalized Medicine and a senior author of the study. […] „This study implicates a potential interplay of chromatin remodeling and mitochondrial metabolism in chordoma genesis,” says Dr. Gai, Director of Bioinformatics, Center for Personalized Medicine, and senior study author.

• #80 Children’s Hospital Los Angeles Team Finds New Potential Causes of Rare and Lethal Bone Cancer | Children’s Hospital Los Angeles

  https://www.chla.org/blog/experts/research-and-breakthroughs/childrens-hospital-los-angeles-team-finds-new-potential-causes

  Genomic study uncovers germline ARID1B and mitochondrial variants potentially driving pediatric chordoma genesis. […] Finding the causes driving the different subtypes of chordoma could lead to the development of better treatment strategies for children, says Katrina OHalloran, MD, MS, pediatric neuro-oncologist and first author of the study. […] Previous chordoma studies revealed the primary genetic defect in one subtype of the diseasepoorly differentiated pediatric chordomais the loss of SMARCB1, a gene that encodes a key member of the SWI/SNF chromatin remodeling complex, which is a group of proteins that associate to remodel the way DNA is packaged within the cell. […] The CHLA research team had previously identified and published strong causal and contributory roles of mitochondrial DNA variants in a variety of pediatric cancers.

• #81 Genetic Clues to Chordoma Etiology: A Protocol to Identify Sporadic Chordoma Patients for Studies of Cancer-Susceptibility Genes | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT01200680/genetic-clues-to-chordoma-etiology-a-protocol-to-identify-sporadic-chordoma-patients-for-studies-of-cancer-susceptibility-genes?mp=s&id=855&slug=chordoma

  Chordoma is a rare, slow growing, often fatal bone cancer derived from remnants of the embryonic notochord. […] Reports of a small number of families worldwide with two or more relatives with chordoma support a role for susceptibility genes in chordoma etiology. […] Although most chordomas are sporadic, we previously identified germline duplication of the T gene (T-dup+), now designated TBXT, which encodes brachyury, a transcription factor that plays an important role in embryonic development, as a major susceptibility mechanism in familial chordoma. A common polymorphism in TBXT is also associated with an increased risk for both familial and sporadic chordoma. […] Thus, a better understanding of predisposing factors and molecular processes in chordoma is critically needed.

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