Gastric cancer tumor tissue samples and cell lines vs normal sample
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33501 | GEO | 2012/11/05
SECONDARY ACCESSION(S): PRJNA148829
REPOSITORIES: GEO
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Project description:We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridisation (aCGH). Gastric cancer tumor tissue samples and cell lines vs normal blood samples
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Project description:Regions of recurrent genomic amplification and deletion are frequently observed in primary gastric cancers (GC). However, identifying specific oncogenes and tumor suppressor genes within these regions can be challenging, as they often cover tens to hundreds of genes. Here, we combined high-resolution array-based comparative genomic hybridization (aCGH) with gene expression profiling to target genes lying within focal high-level amplifications in GC cell lines, and identified RAB23 as an amplified and overexpressed Chr 6p11p12 gene in Hs746T cells. High RAB23 protein expression was also observed in some lines lacking RAB23 amplification, suggesting additional mechanisms besides gene amplification for up-regulating RAB23. siRNA silencing of RAB23 reduced the invasive potential of both amplified and nonamplified GC cell lines. RAB23 gene amplifications were observed in 13% of primary gastric carcinomas. In two independent patient cohorts, RAB23 transcript and protein expression was significantly associated with diffuse-type gastric cancer (dGC) compared to intestinal-type gastric cancer (iGC), providing further evidence that dGC and iGC likely represent two molecularly distinct tumor types. Our study demonstrates that investigating focal chromosomal amplifications by combining highresolution aCGH with expression profiling is a powerful general strategy for identifying novel cancer genes in recurrent regions of chromosomal aberration. Keywords: gastric cancer cell lines, comparative genomic hybridization, gene expression profiling Affy 100K SNP profiling and 32K BAC Array profiling for 7 Gastric Cancer Cell Lines
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Project description:Purpose: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently the number of clinical trials has been very limited due to the small numbers of patients. Chemotherapy regimens are currently rather arbitrarily chosen between either a colorectal (CRC) or a gastric cancer (GC) regimen. Chromosomal copy number aberrations are a hallmark of solid tumours and can be measured by array comparative genomic hybridization (aCGH). The aim of the present study is to investigate whether genome-wide copy number aberrations of SBA are more similar to CRC or GC in order to support treatment of SBA according to either regimen. Experimental Design: A total of 85 GCs, CRCs and SBAs were selected from existing in house aCGH datasets based on array quality and clinical parameters. Differences and similarities in gains and losses of the three tumor types were analyzed using supervised and unsupervised analysis. Results: Hierarchical clustering revealed substantial overlap of chromosomal copy number profiles between SBA and CRC and less overlap between SBA and GC. Chromosome 13q13.2-q31.3 is primarily gained in SBA and CRC and the strongest feature discriminating SBA from GC. Further strong discriminating copy number characteristics are aberrations at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1 and 17p13.3-p13.2. Conclusions: SBA is more similar to CRC than to GC, based on genome-wide copy number aberrations. These data provide molecular support for treatment of SBA according to a CRC regimen. 29 gastric adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control samples, 29 colorectal adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control, 27 small bowel adenocarcinomas done on 30K oligonucleotide arrays of which 2 samples are also done on 5K BAC arrays as control.
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Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 244K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 10 gastric cancer patients.
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