Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genotyping of human neuroblastic tumor NB99

ABSTRACT: The genetic aberrations of NB tumor NB99 were determined using the Affymetrix SNP chip 50K array (Hind III). Experiment Overall Design: DNA copy number change of NB tumor NB99

ORGANISM(S): Homo sapiens

SUBMITTER: Olivier Delattre

PROVIDER: E-GEOD-12461 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.

Janoueix-Lerosey Isabelle I Lequin Delphine D Brugières Laurence L Ribeiro Agnès A de Pontual Loïc L Combaret Valérie V Raynal Virginie V Puisieux Alain A Schleiermacher Gudrun G Pierron Gaëlle G Valteau-Couanet Dominique D Frebourg Thierry T Michon Jean J Lyonnet Stanislas S Amiel Jeanne J Delattre Olivier O

Nature 20081001 7215

Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus enc ...[more]

PMID: 18923523

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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

Genotyping of human neuroblastic tumor NB99

Publications

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.

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