Rare germline variations in familial melanoma
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PROVIDER: PRJNA335673 | ENA |
REPOSITORIES: ENA
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Project description:Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and SNP arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanoma-prone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g. PARP1, CDKN2A) or co-segregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare co-segregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.
2016-12-01 | GSE85010 | GEO
Project description:<p>Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and SNP arrays to characterize CNVs in 113 individuals (105 melanoma cases) from American melanoma-prone families. We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g. PARP1, CDKN2A) or co-segregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare co-segregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.</p>
| phs001177 | dbGaP
Project description: Not available
| S-EPMC5123914 | biostudies-literature
Project description:Rare germline copy number variations and disease susceptibility in familial melanoma
| PRJNA336003 | ENA
Project description:Background: Familial melanoma accounts for 10% of cases, withCDKN2A being the main high-risk gene. However, the mechanisms underlying melanomagenesis in individuals at high risk of developing melanoma remain poorly understood. Objective: To analyze the transcriptome of melanocyte/keratinocyte co-cultures derived from healthy skin from familial melanoma patients vs. controls, to comprehend melanoma development. Methods: Primary melanocyte-keratinocyte co-cultures were established from healthy skin biopsies from 16 unrelated familial melanoma patients (8 CDKN2A mutant, 8 CDKN2A wild-type) and from 7 healthy controls. Whole transcriptome was captured using the SurePrint G3 Human Microarray. Transcriptome analyses included: differential gene expression, functional enrichment, and protein-protein interaction (PPI) networks. Results: We identified a gene profile associated with familial melanoma independently of CDKN2A germline status. Functional enrichment analysis of this profile showed a downregulation of pathways related to DNA repair and immune response in familial melanoma (P < 0.05). In addition, the PPI network analysis revealed a network that consisted of double stranded DNA repair genes (including BRCA1, BRCA2, BRIP1, and FANCA), immune response genes and regulation of chromosome segregation. The hub gene was BRCA1. Conclusion: The constitutive deregulation of BRCA1 pathway genes and immune response in healthy skin could be a mechanism related with melanoma risk.
2022-11-02 | GSE160902 | GEO
Project description: Not available
| S-EPMC5886297 | biostudies-literature
Project description: Not available
| S-EPMC4698275 | biostudies-literature
Project description:Familial pheochromocytoma (PCC) has been associated with germline mutations in 14 genes. Here we investigated three siblings, who presented with (metastatic) bilateral pheochromocytomas, renal oncocytoma, and erythrocytosis. By SNP-array on one patient’s germline DNA a large complex genomic alteration was identified encompassing the intragenic and promoter regions of Myc-Associated Factor X (MAX) and alpha-(1,6)-fucosyltransferase (FUT8). The alteration was confirmed in all patients, as well as loss of the wild type MAX and FUT8 alleles and corresponding loss of protein expression. Uniparental disomy of chromosome 14q, previously demonstrated as a hallmark for MAX-related PCC, was also shown in the index patient by SNP-array. Our results indicate that large genomic deletions of MAX should be considered in familial and bilateral PCC with prior negative testing for gene mutations. In addition, MAX appears to be a new tumor suppressor gene for renal oncocytomas. SNP array was performed for 2 samples: 1 tumor DNA sample and 1 corresponding germline DNA sample
2015-05-13 | E-GEOD-68794 | biostudies-arrayexpress
Project description:DNA methylation variations in familial female and male breast cancer
| PRJNA643525 | ENA