Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiling of brain metastatic melanoma cell lines

ABSTRACT: Cerebral metastases occur in a majority of metastatic melanoma patients and are a major cause of mortality. Despite this, there is a poor understanding of the molecules/pathways that lead to the brain-metastatic phenotype. Studies designed to address this deficiency and test novel therapeutic approaches have until recently been slowed by an absence of preclinical models of spontaneous CNS metastatic melanoma disease. To address this, we isolated two variants of the human melanoma cell line WM239 (named 131/4-5B1 and 131/4-5B2) which can metastasize spontaneously to brain parenchyma from an orthotopic primary transplant. We have performed gene expression profiling on both brain metastatic cell lines (131/4-5B1 and 131/4-5B2) and compared to the poorly metastatic parental cell line WM239A and a derived highly metastatic variant 113/6-4L in order to examine the mechanisms that influence the progression of malignant melanoma to a brain-metastatic phenotype. Two-condition experiment, brain metastatic cell lines (131/4-5B1 and 131/4-5B2) and compared to the poorly metastatic parental cell line WM239A and a derived highly metastatic variant 113/6-4L. Biological replicates: 4 independently grown and harvested cell line passages. Two technical replicate per condition (including dye swap).

ORGANISM(S): Homo sapiens

SUBMITTER: Andre Nantel

PROVIDER: E-GEOD-23601 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Roles for endothelin receptor B and BCL2A1 in spontaneous CNS metastasis of melanoma.

Cruz-Muñoz William W Jaramillo Maria L ML Man Shan S Xu Ping P Banville Myriam M Collins Catherine C Nantel Andre A Francia Giulio G Morgan Sherif S SS Cranmer Lee D LD O'Connor-McCourt Maureen D MD Kerbel Robert S RS

Cancer research 20120803 19

Metastatic spread of melanoma to the central nervous system (CNS) is a common and devastating manifestation of disease progression, which, despite its clinical importance, remains poorly understood with respect to underlying molecular mechanisms. Using a recently developed preclinical model of spontaneous melanoma CNS metastasis, we have identified alterations in expression of endothelin receptor B (EDNRB) as a potential factor that influences brain metastatic potential. Induced overexpression o ...[more]

PMID: 22865454

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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

Gene expression profiling of brain metastatic melanoma cell lines

Publications

Roles for endothelin receptor B and BCL2A1 in spontaneous CNS metastasis of melanoma.

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