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Series GSE43934 Query DataSets for GSE43934
Status Public on Jul 01, 2014
Title Whole Genome Characterization of Circulating Tumor Cells Identifies Novel Prognostic Genomic Alterations in Melanoma Metastasis
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
SNP genotyping by SNP array
Summary 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.
Overall design 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.
Contributor(s) Chiu CG, Nakamura Y, Chong KK, Huang SK, Kawas N, Triche T, Elashoff D, Kiyohara E, Irie RF, Morton DL, Hoon DS
Citation(s) 24718909
Submission date Jan 30, 2013
Last update date Nov 27, 2018
Contact name Neal Percy Kawas
Organization name John Wayne Cancer Institute
Department Molecular Oncology
Street address 2200 Santa Monica Blvd
City Santa Monica
State/province CA
ZIP/Postal code 90404
Country USA
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (88)
GSM1074602 S662_CTC
GSM1074603 T111_Tissue
GSM1074604 T116_CTC
BioProject PRJNA188208

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43934_RAW.tar 6.0 Gb (http)(custom) TAR (of CEL, CHP, CNCHP)
Processed data included within Sample table
Processed data provided as supplementary file

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