Dataset Information

DNA methylation profile from three pairs of melanoma cell lines (WM115/W226-4 ; M4Be/M4BeS2 ; M4Be/TW12)

ABSTRACT: DNA methylation profile from three pairs of cell lines (WM115/W226-4 ; M4Be/M4BeS2 ; M4Be/TW12) with common genetic background (human) and derived in tree different organisms (human-rat-mouse) were analysed by Infinium Human Methylation 450 K bead arrays (Illumina Inc., San Diego, CA). The WM-115 cell line was derived from a human primary melanoma in early stage of vertical growth phase (VGP). The WM-266-4 cell line was derived from a cutaneous metastatic site of a malignant melanoma. The M4Be melanoma cell line was established from a human metastatic lymph node. The TW12 cell line is an aggressive variant of the parental M4Be cell line that was obtained in vivo after two serial transplantations (subcutaneous xenografts in new-born immuno-deprived rats). A subclone (TW12) was selected after limit dilutions for its high ability to form lung metastasis. Briefly, M4Be cells were xenografted intravenously in nude mice. Lung metastases were collected, shortly grown in vitro and used for a second cycle of intravenous injection. Lung metastases were collected and established in vitro as the M4BeS2 cell line.

ORGANISM(S): Homo sapiens

PROVIDER: GSE155856 | GEO | 2022/10/05

REPOSITORIES: GEO

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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

DNA methylation profile from three pairs of melanoma cell lines (WM115/W226-4 ; M4Be/M4BeS2 ; M4Be/TW12)

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