Sequencing melanoma germlines
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001002081 | EGA |
REPOSITORIES: EGA
Similar Datasets
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:The main genetic factors for familial melanoma remain unknown in more than 75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain less than 3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3 and 6 families with 2, 3 and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4 and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD>1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409) and 11q13.3-q21 (max. TLOD 2.654). Future next generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.
2019-01-01 | GSE109207 | GEO
Project description:The main genetic factors for familial melanoma remain unknown in more than 75% of families. CDKN2A is mutated in around 20% of melanoma-prone families. Other high-risk melanoma susceptibility genes explain less than 3% of families studied to date. We performed the first genome-wide linkage analysis in CDKN2A-negative Spanish melanoma-prone families to identify novel melanoma susceptibility loci. We included 68 individuals from 2, 3 and 6 families with 2, 3 and at least 4 melanoma cases. We detected a locus with significant linkage evidence at 11q14.1-q14.3, with a maximum het-TLOD of 3.449 (rs12285365:A>G), using evidence from multiple pedigrees. The genes contained by the subregion with the strongest linkage evidence were: DLG2, PRSS23, FZD4 and TMEM135. We also detected several regions with suggestive linkage evidence (TLOD>1.9) (1q, 6p, 7p, 11q, 12p, 13q) including the region previously detected in melanoma-prone families from Sweden at 3q29. The family specific analysis revealed three loci with suggestive linkage evidence for family #1: 1q31.1-q32.1 (max. TLOD 2.447), 6p24.3-p22.3 (max. TLOD 2.409) and 11q13.3-q21 (max. TLOD 2.654). Future next generation sequencing studies of these regions may allow the identification of new melanoma susceptibility genetic factors.
2019-01-01 | GSE109206 | GEO
Project description:We investigated if the presence of germline CDKN2A mutations or the occurrence of cutaneous melanoma could induce constitutive genome-wide DNA methylation changes. We analyzed the leukocytes’ methylomes of eight patients carrying CDKN2A mutations, eight sporadic melanoma patients and compared them with healthy controls (n=8). The genome-wide DNA methylation profiling was obtained using the Infinium HumanMethylation450 BeadChip platform (Illumina).
2014-09-15 | GSE54939 | GEO
Project description:Inherited genetic risk factors play an important role in cancer. However, other than cancer susceptibility genes found in familial cancer syndromes and inherited in a Mendelian fashion, little is known about modifier genes (germline variants that interact with each other and with environmental factors) that contribute to individual susceptibility. Here we develop a strategy âparental strain expression mappingâ (PSEM), which utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses, to directly identify candidate germline modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with findings in murine models, the expression of the glycolysis pathway was strongly enriched in the non-cancer prostate tissue from patients with prostate cancer who did not recur after surgical resection. Together these data suggest that PSEM can directly identify germline modifier pathways of relevance to human disease. Experiment Overall Design: mRNA expression profiling was carried out with 24 samples of VP from 6 inbred strains.
2008-06-15 | E-GEOD-7270 | biostudies-arrayexpress
Project description:63 melanoma cell lines hybridized to Affymetrix Hu133_Plus 2 oligo arrays. The aim of this study was to identify potential downstream targets of key oncogenes and TSGs in melanoma (including p14ARF, p16INK4A, BRAF etc). Publications relevant to this series include:; Johansson et al. Pigment Cell Res 2007. Experiment Overall Design: 63 melanoma cell lines hybridized to Affymetrix Hu133_Plus 2 oligo arrays. These cell lines were sequenced for key tumour suppressor genes (TSGs) and oncogenes known to be involved in melanoma development. The microarray data was then analysed together with a particular genotype status (see relevant publications) to identify genes that potentially act downstream of these oncogenes and TSGs to contribute to melanoma development. See publications for analysis methods.
2008-06-15 | E-GEOD-7127 | biostudies-arrayexpress
Project description:Germline mutations in CDKN2A and/or red hair colour variants in MC1R genes are associated with an increased susceptibility to develop cutaneous melanoma. To investigate the impact of germinal p.G101W CDKN2A mutation and MC1R variants on gene expression and transcription profiles associated to skin cancer and melanoma in particular, we set-up primary skin cultures from twins belonging to the melanoma prone-families with and without these genomic features. were analyzed using expression array methodology. Overall, 1535 transcripts were deregulated in CDKN2A mutated cells, finding overexpression of immunity-related genes (HLA-DPB1, CLEC2B, IFI44, IFI44L, IFI27, IFIT1, IFIT2, SP110 and IFNK) and downregulation of genes playing a role in the Notch signaling pathway. 3570 transcripts were deregulated in carriers of MC1R variants. In this case, upregulated genes were involved in oxidative stress and DNA damage pathways as well as in neurodegenerative diseases such as Parkinson’s, Alzheimer and Huntington. In contrast, downregulated genes were associated with pigmentation synthesis/transport and angiogenesis. By using a coculture system, this study identified key molecular functions and/or pathways that are deregulated due to alterations in melanoma susceptibility genes which in turn, could be involved in initiation/progression of the disease. 12 samples total. Several experimental groups: with and without genomic features (CDKN2A, MC1R).
2013-12-31 | E-GEOD-44805 | biostudies-arrayexpress
Project description:n this project we have sequenced the transcriptome of several comonly used mouse melanoma cell lines. Our aim is to understand what mutations and rearrangements are found in these cell lines to gain a better understanding of the genes that contribute to melanomagenesis. As these cell lines are used as models of melanoma these sequences represent an important resource for functional studies. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2015-01-17 | E-ERAD-94 | biostudies-arrayexpress
Project description:Inherited genetic risk factors play an important role in cancer. However, other than cancer susceptibility genes found in familial cancer syndromes and inherited in a Mendelian fashion, little is known about modifier genes (germline variants that interact with each other and with environmental factors) that contribute to individual susceptibility. Here we develop a strategy “parental strain expression mapping” (PSEM), which utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses, to directly identify candidate germline modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with findings in murine models, the expression of the glycolysis pathway was strongly enriched in the non-cancer prostate tissue from patients with prostate cancer who did not recur after surgical resection. Together these data suggest that PSEM can directly identify germline modifier pathways of relevance to human disease. Keywords: genetic modifier
2007-10-12 | GSE7270 | GEO
Project description:Most cancer genomics papers to date have focused on aberrations in genomic DNA and protein-coding transcripts. However, around 50% of transcripts have no coding potential and may exist as non-coding RNA. We performed RNA-seq in BRAFv600e melanoma skin cancer and on melanocytes over-expressing oncogenic BRAF to catalog transcriptome remodeling. We discovered that BRAF regulates expression of 1027 protein coding transcripts, 39 annotated lncRNAs and 70 novel transcripts. Many of the novel transcripts are lncRNAs. We used an indepenedent dataset to interrogate our novel transcripts and found that the novel lncRNA BANCR is a BRAF-regulated lncRNA recurrently upregulated in melanoma. Knockdown of BANCR impairs melanoma cell migration.
2012-04-28 | GSE37132 | GEO