Ena-DATASET-PICR-28-07-2014-16:03:44:569-506 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001000944 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:NGS of 10 mucosal melanomas:
Whole genome sequencing of 5 mucosal melanomas and matched normal DNA
Whole exome sequencing of 5 mucosal melanomas and matched normal DNA
| EGAD00001000945 | EGA
Project description:We performed microRNA sequencing of primary human FFPE Acral Melanoma (AM), Cutaneous Melanoma (CM), Acral Nevi (AN), and Cutaneous Nevi (CN). We found that previously identified ratios of microRNAs, particularly miR-21-5p and miR-211-5p, were able to accurately classify benign and malignant melanocytic neoplasia, both in non-acral cutaneous melanomas and nevi (CM vs CN), as well as matched acral melanoma and nevi (AM vs AN). Receiver operating characteristic area under the curve (AUC) of Ensemble models trained using these microRNA ratios demonstrated AUCs of 0.88-0.90 across these melanoma subtypes, suggesting the potential utility of these ratios as a biomarker of malignancy in melanocytic neoplasia.
2024-08-14 | GSE266413 | GEO
Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
2022-01-12 | PXD027968 | Pride
Project description:Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed), and skin with chronic sun-induced damage have infrequent mutations in BRAF and NRAS, genes within the mitogenactivated protein (MAP) kinase pathway commonly mutated in melanomas on intermittently sun-exposed skin. This raises the question of whether other aberrations are occurring in the MAP kinase cascade in the melanoma types with infrequent mutations of BRAF and NRAS. Oncogenic mutations in KIT were found in three of seven tumors with amplifications. Examination of all 102 primary melanomas found mutations and/or copy number increases of KIT in 39% ofmucosal, 36% of acral, and 28% of melanomas on chronically sun-damaged skin, but not in any (0%) melanomas on skin without chronic sun damage. Seventy-nine percent of tumors with mutations and 53% of tumors with multiple copies of KIT demonstrated increased KIT protein levels. KIT is an important oncogene in melanoma. Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden. Keywords: melanoma, oncogene, comparative genomic hybridization, KIT
2006-09-09 | GSE4747 | GEO
Project description:Whole exome sequencing of 41 melanomas and normal DNA from Braf mutant mice: 15 tumours from UV exposed mice, 15 tumours from non-exposed mice and 11 from UV exposed, sunscreen-protected mice.
| EGAD00001000775 | EGA
Project description:We compared genome-wide DNA copy number alterations and mutational status in BRAF and RAS genes of 126 primary melanomas arising in four groups in which UV exposure differ: skin with (n=30), and without chronic sun damage (n=40); palms, soles and subungual (acral) sites (n=36) (which have very little sun exposure); and mucosa (n=20) (no sun exposure).
2010-06-09 | E-GEOD-2631 | biostudies-arrayexpress
Project description:Cutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5’-UTR (HNRNPUL1, CCDC77, PES1), and 3’-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.
2017-12-01 | GSE80435 | GEO
Project description:Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity.
| S-EPMC6463754 | biostudies-literature
Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails3. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
2022-01-17 | GSE181748 | GEO
Project description:A substantial part of cutaneous malignant melanomas develops from benign nevi. However, the precise molecular events driving the transformation from benign to malignant melanoma are not well understood. We used laser microdissection and mass spectrometry to analyze the proteomes of melanoma subtypes, including superficial spreading melanomas (SSM, n=17), nodular melanomas (NM, n=17), and acral melanomas (AM, n=15). Furthermore, we compared the proteomes of nevi cells and melanoma cells within the same specimens (nevus-associated melanoma (NAM, n=14)). In total, we quantified 7,935 proteins. Despite the genomic and clinical differences of the melanoma subtypes, our analysis revealed relatively similar proteomes, except for the upregulation of proteins involved in immune activation in NM vs AM. Examining NAM versus nevi, we found 1,725 differentially expressed proteins. Among these proteins were 140 that overlapped with cancer hallmarks, tumor suppressors, and regulators of metabolism and cell cycle. Pathway analysis indicated aberrant activation of the RAS/MAPK and PI3K-AKT-mTOR pathways, as well as the Hippo-YAP pathway. Using a classifier, we identified six proteins capable of distinguishing melanoma from nevi samples. Our study represents the first comprehensive comparative analysis of the proteome in melanoma subtypes and associated nevi, offering new insights into the biological behavior of these distinct entities.
2024-01-28 | PXD044107 | Pride