Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive Analysis of the DNA Methylome of Human Cutaneous Melanoma

ABSTRACT: Novel screening techniques are allowing the depiction of the portraits of molecular alterations across cancer types, enabling a better understanding of the progression mechanisms and providing new therapeutic targets. Here, we performed an unbiased genome-wide DNA methylation analysis to interrogate the epigenetic events characterizing melanoma progression and prognosis, on a discovery cohort of clinical specimens. Our data underscores the importance of epigenetic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation programs unleashes malignant dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor progression previously unrelated with melanoma, and determined a survival prognostic signature with potential clinical applicability. All findings were validated in independent clinical cohorts and cross-correlated with publicly available databases, highlighting the relevance of the identified DNA methylation alterations for melanoma progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86355 | GEO | 2017/06/23

SECONDARY ACCESSION(S): PRJNA341510

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteomic profiling of exosomes isolated from invasive and proliferative melanoma cell lines and correlation with exosomes from plasma of human melanoma patients pre- and post-checkpoint inhibitor treatment

Project description:Over the last decades, exosomes have received increasing attention due to their involvement in numerous pathologies including cancer. Tumor-derived exosomes and exosomes derived from the tumor microenvironment are implicated in multiple mechanisms that support disease progression such as the escape of malignant cells from immunosurveillance, tumor cell growth, tumor angiogenesis, preparation of a pre-metastatic niche and remodeling of the extracellular matrix, thereby promoting dissemination and metastasis. Here, we performed protein expression phenotyping of exosomes derived from different invasive and proliferative melanoma cell lines (n=8) to provide a solid framework of gene expression programs, which - in a clinical setting - would be useful for prognosis and may also predict treatment response. Cell line characteristics have been published previously (Wenzina et al.,2020). Having identified a set of differentially expressed proteins in proliferative and invasive melanoma cell lines, we correlated them to the protein composition of plasma exosomes from melanoma patients pre and post immunotherapy treatment (n=7) as well as healthy controls (n=5).

2022-07-14 | PXD025475 | Pride

Peripheral positioning of lysosomes supports melanoma aggressiveness

Project description:Emerging evidences suggest that both function and position of organelles are pivotal for tumor cell dissemination. Among them, lysosomes stand out as they integrate metabolic sensing with gene regulation and secretion of proteases. Yet, how lysosomes function is linked to their position and thereby control metastatic progression remains elusive. Here, we analyzed lysosome subcellular distribution in micropatterned patient-derived melanoma cells and found that lysosome spreading scales with their aggressiveness. Peripheral lysosomes promote invadopodia-based matrix degradation and invasion of melanoma cells which is directly linked to their lysosomal and cell transcriptional programs. When controlling lysosomal positioning using chemo-genetical heterodimerization in melanoma cells, we demonstrated that perinuclear clustering impairs lysosomal secretion, matrix degradation and invasion. Impairing lysosomal spreading in a zebrafish metastasis model significantly reduces invasive outgrowth. Our study provides a mechanistic demonstration that lysosomal positioning controls cell invasion, illustrating the importance of organelle adaptation in carcinogenesis.

2023-07-31 | E-MTAB-13165 | biostudies-arrayexpress

Chromatin remodellers Brg1 and Bptf are required for normal gene expression and progression of oncogenic Braf-driven mouse melanoma [ChIP-seq]

Project description:Somatic oncogenic mutation of BRAF coupled with inactivation of PTEN constitute a frequent combination of genomic alterations driving development of human melanoma. Mice genetically engineered to conditionally express oncogenic BrafV600E and inactivate Pten in melanocytes following tamoxifen treatment rapidly develop melanoma. While early stage melanomas comprised melanin-pigmented Mitf and Dct-expressing cells, expression of these and other melanocyte identity genes was lost in later stage tumours that showed histological and molecular characteristics of de-differentiated neural crest type cells. Melanocyte identity genes displayed loss of active chromatin marks and RNA polymerase II and gain of heterochromatin marks indicating epigenetic reprogramming during tumour progression. Nevertheless, late stage tumour cells grown in culture re-expressed Mitf and melanocyte markers and Mitf together with Sox10 co-regulated a large number of genes essential for their growth. In this melanoma model, somatic inactivation that the catalytic Brg1 (Smarca4) subunit of the SWI/SNF complex and the scaffolding Bptf subunit of the NuRF delayed tumour formation and deregulated large and overlapping gene expression programs essential for normal tumour cell growth. Moreover, we show that Brg1 and Bptf co-regulated many genes together with Mitf and Sox10. Together these transcription factors and chromatin remodelling complexes orchestrate essential gene expression programs in mouse melanoma cells

2019-04-17 | GSE100998 | GEO

miR-146a Exerts Differential Effects on Melanoma Growth and Metastatization.

Project description:Malignant melanoma is the most aggressive form of skin cancer therefore it is crucial to disclose its underlying molecular mechanisms. MicroRNAs are small endogenous non-coding RNAs able to post-transcriptionally down-regulate the expression of direct target genes. Using a melanoma progression model, we identified miR-146a as a key double-acting player in melanoma malignancy. In fact, miR-146a is able to enhance tumor growth while it suppresses dissemination. We evidenced that melanoma cell growth is coordinated by its direct target lunatic fringe (LFNG) which operates on the NOTCH/PTEN/Akt pathway. Instead, metastasis formation inhibition is linked to decreased expression of ITGAV and ROCK1. Relevantly, miR-146a expression correlates with melanoma recurrence and it is enriched both in patients-derived melanoma and cutaneous metastasis samples, while its direct targets are depleted. However, miR-146a levels drop in Circulating Tumor Cells, suggesting the necessity for miR-146a expression to fluctuate during tumor progression in order to favor tumor growth and allow dissemination. This study reconciles the contradictory biological functions of miR-146a in melanoma progression and unravels distinct molecular mechanisms that need to be considered for therapeutic interventions.

2016-03-18 | GSE77090 | GEO

Homo sapiens

Project description:Clinical relevance of SKP2 alterations in metastatic melanoma

| PRJNA129247 | ENA

Stromal Changes in The Aged Lung Induce an Emergence From Melanoma Dormancy

Project description:Disseminated cancer cells (DCCs) that escape the primary site can seed in distal tissues, but may take several years, or even decades to grow out into overt metastases, a phenomenon termed tumor dormancy. Despite its importance in metastasis and residual disease, few studies have been able to successfully model or characterize dormancy within melanoma. Here, we show that age-related changes in the lung microenvironment facilitate a permissive niche for efficient outgrowth of disseminated dormant tumor cells, in contrast to the aged skin, where age-related changes suppress melanoma growth but drive dissemination. A model of melanoma progression that addresses these microenvironmental complexities is the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1-3. We have previously shown that dermal fibroblasts are key orchestrators of promoting phenotype switching in primary melanoma tumors via changes in the secretion of soluble factors during aging4-8. Our new data identifies Wnt5A as a master regulator of activating melanoma DCC dormancy within the lung, which initially enables efficient dissemination and seeding of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble Wnt antagonist sFRP1, which inhibits Wnt5A, enabling efficient metastatic outgrowth. Further, we have identified the tyrosine kinase receptors AXL and MER as promoting a dormancy-toreactivation axis respectively. Overall, we find that age-induced changes in distal metastatic microenvironments promotes efficient reactivation of dormant melanoma cells in the lung.

2022-03-03 | MSV000088977 | MassIVE

Genome-wide promoter methylation analysis associated with malignant melanoma progression

Project description:Epigenetic alterations play significant roles in the melanoma tumorigenesis and malignant progression. We profiled genome-wide promoter DNA methylation patterns of melanoma cells deribed from primary lesions of Radial Growrth phase (RGP) and Vertical Growth Phase (VGP), metastatic lesions, and primary normal melanocytes by interrogating 14,495 genes using Illumina bead chip technology. By comparative analysis of the promoter methylation profiles, we identified epigenetically silenced gene signatures that potentially associated with malignant melanoma progression. Bisulphite converted genomic DNA from a group of melanoma cells representing pathologic stages of melanoma progression (3 cell lines derived from RGP melanoma lesions, 4 cell lines derived from VGP lesions, and 3 melastatic melanomas) and normal human primary melanocytes isolated from lightly pigmented adult skin were hybridized to Illumina's Infinium HumanMethylation27 BeadChips

2013-12-20 | E-GEOD-53516 | biostudies-arrayexpress

Molecular changes induced by melanoma cell conditioned medium (MCM) in HUVEC cells.

Project description:Malignant melanoma is a complex genetic disease and the most aggressive form of skin cancer. Melanoma progression and metastatic dissemination fundamentally relies on the process of angiogenesis. Melanomas produce an array of angiogenic modulators that mediate pathological angiogenesis. Such tumor-associated modulators arbitrate the enhanced proliferative, survival and migratory responses exhibited by endothelial cells, in the hypoxic tumor environment. The current study focuses on melanoma-induced survival of endothelial cells under hypoxic conditions. Melanoma conditioned media were capable of enabling prolonged endothelial cell survival under hypoxia, in contrast with the conditioned media derived from melanocytes, breast and pancreatic tumors. To identify the global changes in gene expression and further characterize the pro-survival pathway induced in endothelial cells, we performed microarray analysis on endothelial cells treated with melanoma conditioned medium under normoxic and hypoxic conditions. Huvec cells were grown in melanoma conditioned medium or DMEM 10% FCS for 12 h under hypoxic or normoxic conditions. In order to identify the transcripts modulated by melanoma CM, samples treated with MCM were compared to those grown in DMEM alone.

2013-09-30 | E-GEOD-33115 | biostudies-arrayexpress

Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WGS

Project description:An incomplete view of the (epi)genetic events that drive melanoma initiation and progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. Recent approaches that integrate human melanoma genomic and transcriptomic data provide unprecedented opportunities to discover oncogenic melanoma drivers. One limitation, however, is that human melanoma genome exhibits a radically altered cytogenetic profile. Hence there is a need for biologically-meaningful approaches to identify and validate lesions that drive melanomagenesis. We combined comparative oncogenomic approaches with mouse modeling to identify new cancer genes/pathways that drive melanoma progression. Spontaneously acquired genetic alterations such as copy-number alterations and specific mutations in mouse tumors of defined genetic origin were identified and used to prioritize relevant lesions from the complex human melanoma genomes. This integrated effort confirmed the importance of several genes and pathways previously implicated in melanoma and identified new putative melanoma tumor suppressor genes. Genetic ablation of one such gene, Fes, cooperated with BRafv600E to accelerate melanomagenesis in mice. This comparative oncogenomic approach has therefore helped discover a series of novel melanoma tumor suppressor genes, including FES, with prognostic and therapeutic relevance in human melanoma.

2017-05-03 | E-MTAB-4921 | biostudies-arrayexpress

Integrative and comparative genomics identifies the tyrosine kinase FES as a key melanoma tumor supppressor: WES

2017-05-03 | E-MTAB-4917 | biostudies-arrayexpress