Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Affymetrix SNP array data for metastatic melanoma specimens

ABSTRACT: Comparison between the copy number of differentially methylated sites between lymph node metastasis from melanoma patients with good prognosis and melanoma brain metastasis. All samples are taken from different patients, and were established as cell lines in the John Wayne Cancer Institute. Sixteen metastatic melanomas were run on Affymetrix Genome-Wide Human SNP Array 6.0. Lymph node metastases and brain metastases genetic copy number variations were compared.

ORGANISM(S): Homo sapiens

SUBMITTER: Dave Hoon

PROVIDER: E-GEOD-44019 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis.

Marzese Diego M DM Scolyer Richard A RA Huynh Jamie L JL Huang Sharon K SK Hirose Hajime H Chong Kelly K KK Kiyohara Eiji E Wang Jinhua J Kawas Neal P NP Donovan Nicholas C NC Hata Keisuke K Wilmott James S JS Murali Rajmohan R Buckland Michael E ME Shivalingam Brindha B Thompson John F JF Morton Donald L DL Kelly Daniel F DF Hoon Dave S B DS

Human molecular genetics 20130906 1

Melanoma brain metastasis (MBM) represents a frequent complication of cutaneous melanoma. Despite aggressive multi-modality therapy, patients with MBM often have a survival rate of <1 year. Alteration in DNA methylation is a major hallmark of tumor progression and metastasis; however, it remains largely unexplored in MBM. In this study, we generated a comprehensive DNA methylation landscape through the use of genome-wide copy number, DNA methylation and gene expression data integrative analysis ...[more]

PMID: 24014427

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Project description:Circulating tumor cells (CTCs) are critical in the development of distant organ tumor metastasis, and are associated with advanced cancer stage and poor patient outcome. Here, we present the first genome-wide nucleotide-level characterization of CTCs. Our single-nucleotide polymorphism (SNP) analysis in patients with melanoma involved: 1) global comparative genomic analysis of CTCs and matched regional metastases, 2) identification of key genomic aberrations in CTCs, 3) verification of these target genes in aggressive distant tumor metastases, and 4) evidence of selective expression and functional consequence of CTC-associated genes in melanomas. We report 131 aberrant loci in CTCs that are potentially pro-metastatic, and show that such expression of a 5-marker gene panel (CSMD2, CNTNAP5, FLJ14051, ADAM6, TRPM2) in melanomas confers prognostic utility. Successful treatment of melanoma requires understanding of the metastatic process and identification of patients with tumors most likely to develop aggressive metastatic disease. Melanomas are heterogeneous, and CTCs have long been recognized as vehicles for cancer spread, representing particularly aggressive tumor clones that can evolve into successful clinical metastases. Elucidation of genomic aberrations in CTCs will aid in the development of prognostic biomarkers and therapeutic strategies to target CTCs to prevent or control distant cancer spread. This study provides the first detailed genomic confirmation of the close relation between CTCs and tumor metastases, and illustrates how CTCs can be utilized as a novel approach and rational source for identification of pro-metastatic genes in cancer research. Three individual patient cohorts were utilized in the study. CNV and LOH loci were evaluated initially in metastatic melanoma patients (n=13) in a discovery cohort. SNP loci that harbored CNV/LOH in CTCs were then separately verified for: (a) presence in distant organ metastasis (AJCC Stage IV melanoma) (n=27), and (b) relevance to prognosis in regional melanoma metastasis (AJCC Stage III melanoma) (n=35). The first discovery patient cohort group was utilized for capture of CTCs, and consisted of peripheral blood mononuclear cell (PBMC) and tumor specimens from metastatic melanoma patients (n=13). CTC-related loci were verified in a second cohort of patients with Stage IV distant organ metastases (n=27), including 15 brain, 4 lung, and 8 gastrointestinal (bowel, liver) metastases. The third patient cohort consisted of early passage (<12) established melanoma cell lines derived from 35 regional melanoma metastases (Stage III) for evaluation of the prognostic utility of the CTC-associated aberrant loci.

Dataset Information

Affymetrix SNP array data for metastatic melanoma specimens

Publications

Epigenome-wide DNA methylation landscape of melanoma progression to brain metastasis reveals aberrations on homeobox D cluster associated with prognosis.

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