Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA92843 | ENA |
REPOSITORIES: ENA
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Project description:Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic naevi
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Project description:Human melanomas frequently harbor amplifications of EZH2. However, the oncogenic contribution of this methyltransferase to melanoma formation has remained elusive. Taking advantage of murine melanoma models, we now show that EZH2 drives tumorigenesis from benign BrafV600E or NrasQ61K-expressing melanocytes. EZH2 oncogenicity results from silencing of genes relevant for the integrity of the primary cilium, a signaling organelle projecting from the surface of vertebrate cells. Consequently, gain of EZH2 function promotes loss of primary cilia in benign melanocytic lesions. In contrast, blockade of EZH2 activity evokes ciliogenesis and cilia-dependent growth inhibition in malignant melanoma. Finally, we demonstrate that loss of cilia enhances pro-tumorigenic WNT/β-catenin signaling and is itself sufficient to drive metastatic melanoma in benign cells. Thus, primary cilia deconstruction is a key process in EZH2-driven melanomagenesis.
2019-04-04 | GSE112677 | GEO
Project description:The molecular properties of benign melanocytic lesions are poorly understood. Only few studies have been performed on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expression of 25 SN and 15 NCN were analyzed. Molecular profiling was done using the RNA NanoString nCounter Gene Expression Platform (No. of genes = 770). Marker discovery was performed with a training set consisting of 7 SN and 7 NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and 8 NCN samples. Using the training set, 197 differentially expressed genes were identified in SN versus NCN. Of these, 74 genes validated in the validation set (FDR Q value ≤ 0.13). In addition, using Random Forest and LASSO feature selection a molecular signature of SN versus NCN was identified including 15 top-ranked genes. Gene set analysis showed upregulation of gene pathways with increased expression of transcripts related to immunomodulatory, inflammatory and extracellular matrix interactions as well as angiogenesis associated processes in SN. Although the molecular characteristics of malignant melanoma have been studied in detail, the molecular properties of benign melanocytic lesions such as common nevocellular nevi (NCN) and Spitz nevi (SN) remain poorly understood. This limited knowledge hinders a better understanding of atypical and malignant transformation of melanocytes. The present study identified a distinct molecular expression profile in SN compared to NCN, even when lesions were obtained from the same patients. These findings strongly indicate that SN represent a distinct group of melanocytic neoplasms and evolve differentially and not sequentially from NCN.
2018-02-15 | GSE110589 | GEO
Project description:Melanoma is the least common form of skin cancer, but accounts for the most deaths. Dermatopathologists face difficult diganostic determinations with a subset of ambiguous melanoma cases. Copy number variation in melanoma can serve as an additional biomarker to distinguish melanoma from benign melanocytic lesions.
2016-04-22 | GSE68476 | GEO
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:Spitzoid neoplasms are a challenging group of cutaneous melanocytic proliferations that occur in children or adolescents but can also arise in the elderly. They are characterized by epithelioid and/ or spindle-shaped melanocytes with a stromal background of variable amounts of lymphocytes, blood vessels and sclerosis. According to the WHO 2018 classification, Spitzoid melanocytic lesions are classified as benign Spitz nevi (SN), atypical Spitz tumors (AST) or malignant Spitz tumors (MST). The intermediate AST category represents a diagnostically challenging group since on purely histopathological grounds, their benign or malignant character remains unpredictable. This results in uncertainties in patient management and prognosis. The molecular properties of Spitzoid lesions, especially their transcriptomic landscape, remain poorly understood and genomic alterations in melanoma-associated oncogenes are typically absent. The aim of this study was to characterize the transcriptome of Spitzoid melanocytic neoplasms with digital mRNA expression profiling. Formalin-fixed-paraffin-embedded samples (including 27 SN, 10 AST and 14 MST) were analyzed using the RNA NanoString nCounter PanCancer Pathways Gene Expression panel. The number of significantly differentially expressed genes in SN vs. MST, SN vs. AST and AST vs. MST was 68, 167 and 18, respectively. Gene set enrichment analysis revealed an upregulation of pathways related to epithelial mesenchymal transition, immunomodulatory-, angiogenesis- as well as myogenesis associated processes in AST and MST. In addition, a specific gene expression signature of SN vs. MST was discovered based on the top-ranked six most informative gene expression markers: NRAS, NF1, BMP2, EIF2B4, IFNA17 and FZD9. The AST samples showed intermediate levels of the identified signature. This implies that the identified gene expression signature can potentially be used to distinguish high-grade from low-grade AST. This combined histopathological and transcriptomic methodology is promising for diagnostics of Spitzoid neoplasms and patient management in dermatological oncology in the future.
2019-10-25 | GSE139314 | GEO
Project description:In the study, researchers investigated acral melanomas, particularly subungual melanomas (SUM), which are primarily characterized by whole genome copy number variations (CNV) such as amplifications, gains, and losses. Previous research has utilized various cytogenetic or molecular analyses ranging from targeted methods focused on specific genes to comprehensive whole genome and whole transcriptome sequencing techniques. To differentiate between malignant and benign lesions, fluorescence in situ hybridization (FISH) methods have been commonly employed, utilizing probes targeting genes like CCND1, RREB1, MYB, CDKN2A, or MYC either individually or in combination.In this study a Comparative Genomic Hybridization on array (array-CGH) was performed to detect whole genome CNV. This approach aimed to improve the classification of malignant and benign lesions in a cohort consisting of 31 SUM cases and 8 subungual lentiginous melanocytic proliferations with or without atypia.
2024-05-31 | GSE262724 | GEO
Project description:Expression of the BRAFV600E oncoprotein is known to cause benign lesions, for example melanocytic nevi (moles). In spite of the oncogenic function of mutant BRAF, these lesions are arrested by a cell-autonomous mechanism called Oncogene-Induced Senescence (OIS). Infrequently, nevi can progress to malignant melanoma, through mechanisms that are incompletely understood. To gain more insight into this vital tumor suppression mechanism, we performed a mass spectrometry-based screening of the proteome and phosphoproteome in cycling and senescent cells as well as cells that have abrogated senescence. Proteome analysis of senescent cells revealed the upregulation of established senescence biomarkers, including specific cytokines, but also several proteins not previously associated with senescence, including extracellular matrix-interacting. Using both general and targeted phosphopeptide enrichment by Ti4+-IMAC and phosphotyrosine antibody enrichment, we identified over 15,000 phosphorylation sites. Among the regulated phosphorylation sites we encountered components of the interleukin, BRAF/MAPK and CDK-retinoblastoma (Rb) pathways and several other factors. The extensive proteome and phosphoproteome dataset of BRAFV600E-expressing senescent cells provides molecular clues as to how OIS is initiated, maintained or evaded, serving as a comprehensive proteomic basis for functional validation.
2015-01-13 | PXD001068 | Pride
Project description:Expression of the BRAFV600E oncoprotein is known to cause benign lesions, for example melanocytic nevi (moles). In spite of the oncogenic function of mutant BRAF, these lesions are arrested by a cell-autonomous mechanism called Oncogene-Induced Senescence (OIS). Infrequently, nevi can progress to malignant melanoma, through mechanisms that are incompletely understood. To gain more insight into this vital tumor suppression mechanism, we performed a mass spectrometry-based screening of the proteome and phosphoproteome in cycling and senescent cells as well as cells that have abrogated senescence. Proteome analysis of senescent cells revealed the upregulation of established senescence biomarkers, including specific cytokines, but also several proteins not previously associated with senescence, including extracellular matrix-interacting. Using both general and targeted phosphopeptide enrichment by Ti4+-IMAC and phosphotyrosine antibody enrichment, we identified over 15,000 phosphorylation sites. Among the regulated phosphorylation sites we encountered components of the interleukin, BRAF/MAPK and CDK-retinoblastoma (Rb) pathways and several other factors. The extensive proteome and phosphoproteome dataset of BRAFV600E-expressing senescent cells provides molecular clues as to how OIS is initiated, maintained or evaded, serving as a comprehensive proteomic basis for functional validation.
2015-01-12 | PXD000523 | Pride
Project description:The implication of epigenetic alterations in the pathogenesis of melanoma is increasingly recognized. Here we performed genome-wide DNA methylation analysis of primary cutaneous melanoma and benign melanocytic naevus interrogating 14,495 genes using beadchip technology. This first genome-wide view of promoter methylation in primary cutaneous melanoma revealed an array of recurrent DNA methylation alterations with potential diagnostic applications. Among 106 frequently hypermethylated genes there were many novel methylation targets and tumor suppressor genes. Highly recurrent methylation of the HOXA9, MAPK13, CDH11, PLEKHG6, PPP1R3C and CLDN11genes was established. Promoter methylation of MAPK13, encoding p38?, was present in 67% of primary and 85% of metastatic melanomas. Restoration of MAPK13 expression in melanoma cells exhibiting epigenetic silencing of this gene reduced proliferation, indicative of tumor suppressive functions. This study demonstrates that DNA methylation alterations are widespread in melanoma and suggests that epigenetic silencing of MAPK13 contributes to melanoma progression. Bisulphite converted genomic DNA from 5 fresh-frozen benign naevus and 24 fresh-frozen primary melanoma biopsy samples were hybridised to Illumina's Infinium HumanMethylation27 Beadchips
2013-04-24 | E-GEOD-45266 | biostudies-arrayexpress