Gene "PDGFRA"
Found 3 records
Gene information
Gene symbol:
PDGFRA
See related:
Ensembl: ENSG00000134853, Gene ID: 5156
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
3
Disorder:
1
Vriant:
3
Reference:
1
Effect type:
Expressivity(3)
Modifier effect:
Risk factor(3)
Details:
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Variant 1:Gene:Genomic location:dbSNP ID:Target disease:Sarcoma(DOID_1115)Effect type:ExpressivityModifier effect:Risk factorEvidence:Pedigree analysisEffect:PDGFRA is a candidate modifier gene.Reference:Title:Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of sarcoma.Species studied:HumanAbstract:BACKGROUND:Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS:We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma. Including the initial family, eight independent sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION:Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary sarcoma. In addition, we identified PDGFRA as a candidate modifier gene.
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Variant 2:Gene:Genomic location:Target disease:Sarcoma(DOID_1115)Effect type:ExpressivityModifier effect:Risk factorEvidence:Pedigree analysisEffect:PDGFRA is a candidate modifier gene.Reference:Title:Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of sarcoma.Species studied:HumanAbstract:BACKGROUND:Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS:We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma. Including the initial family, eight independent sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION:Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary sarcoma. In addition, we identified PDGFRA as a candidate modifier gene.
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Variant 3:Gene:Genomic location:Target disease:Sarcoma(DOID_1115)Effect type:ExpressivityModifier effect:Risk factorEvidence:Pedigree analysisEffect:PDGFRA is a candidate modifier gene.Reference:Title:Germline CDKN2A/P16INK4A mutations contribute to genetic determinism of sarcoma.Species studied:HumanAbstract:BACKGROUND:Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS:We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma. Including the initial family, eight independent sarcoma cases carried a germline mutation in the CDKN2A/p16INK4A gene. In five out of seven formalin-fixed paraffin-embedded sarcomas, heterozygosity was lost at germline CDKN2A mutations sites demonstrating complete loss of function. As sarcomas are rare in CDKN2A/p16INK4A carriers, we searched in constitutional WES of nine carriers for potential modifying rare variants and identified three in platelet-derived growth factor receptor (PDGFRA) gene. Molecular modelling showed that two never-described variants could impact the PDGFRA extracellular domain structure. CONCLUSION:Germline mutations in CDKN2A/P16INK4A, a gene known to predispose to hereditary melanoma, pancreatic cancer and tobacco-related cancers, account also for a subset of hereditary sarcoma. In addition, we identified PDGFRA as a candidate modifier gene.