Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Tissue samples from the same individual patient

ABSTRACT: We searched for putative phenotypic and genotypic differences between primary lesions and melanoma metastasis. Therefore we investigated melanoma cells derived either from the primary tumor or from lymph node metastasis of the same individual patient. In vitro studies revealed high migratory and anchorage independent growth of metastasis-derived cells. Unexpectedly, whole genome DNA analysis displayed a total of 10 homozygous losses in the primum-derived cell line, whereas the metastasis–derived cell line only shared 5 of those losses. We further tested these cells in a mouse model for intradermal melanoma growth and detected fast growth of the metastasis-derived cell line and no growth of primum-derived cells. Therefore we suggest that tumor cell progression at the metastatic niche can occur parallel and independently from the primary tumor. Additionally we screened melanoma samples isolated from patients and could identify one case were the primum harboured deletions not present in the metastatic lesion. We propose that for mutation-targeted therapy genotyping should be performed not only from primary, but foremost from metastatic melanoma cells. Blood samples as well tumor samples were directly processed for DNA isolation and subsequent chip hybridization. Each sample was hybridized onto a single affymetrix SNP 6.0 chip.

ORGANISM(S): Homo sapiens

SUBMITTER: Mario Mikula

PROVIDER: E-GEOD-26053 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of genetic disparity between primary and metastatic melanoma in human patients.

Swoboda Alexander A Rasin-Streden Doris D Schanab Oliver O Okamoto Ichiro I Pehamberger Hubert H Petzelbauer Peter P Mikula Mario M

Genes, chromosomes & cancer 20110516 9

It is commonly accepted that cancer cell progression is accompanied by accumulation of genetic changes. Here we searched for copy number variations in melanoma and asked whether homozygous losses always cumulate during tumor cell progression. Therefore we investigated either melanoma cell lines or tissue derived from the primary lesion and from the lymph node metastasis of the same individual patient. In vitro studies of melanoma cell lines revealed high migratory and anchorage independent growt ...[more]

PMID: 21584902

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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

Tissue samples from the same individual patient

Publications

Identification of genetic disparity between primary and metastatic melanoma in human patients.

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