DNA Copy Number Alterations (dna + copy_number_alteration)

Distribution by Scientific Domains


Selected Abstracts


High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2006
Cathie Garnis
Abstract Chromosomal regions harboring tumor suppressors and oncogenes are often deleted or amplified. Array comparative genomic hybridization detects segmental DNA copy number alterations in tumor DNA relative to a normal control. The recent development of a bacterial artificial chromosome array, which spans the human genome in a tiling path manner with >32,000 clones, has facilitated whole genome profiling at an unprecedented resolution. Using this technology, we comprehensively describe and compare the genomes of 28 commonly used non-small cell lung carcinoma (NSCLC) cell models, derived from 18 adenocarcinomas (AC), 9 squamous cell carcinomas and 1 large cell carcinoma. Analysis at such resolution not only provided a detailed genomic alteration template for each of these model cell lines, but revealed novel regions of frequent duplication and deletion. Significantly, a detailed analysis of chromosome 7 identified 6 distinct regions of alterations across this chromosome, implicating the presence of multiple novel oncogene loci on this chromosome. As well, a comparison between the squamous and AC cells revealed alterations common to both subtypes, such as the loss of 3p and gain of 5p, in addition to multiple hotspots more frequently associated with only 1 subtype. Interestingly, chromosome 3q, which is known to be amplified in both subtypes, showed 2 distinct regions of alteration, 1 frequently altered in squamous and 1 more frequently altered in AC. In summary, our data demonstrate the unique information generated by high resolution analysis of NSCLC genomes and uncover the presence of genetic alterations prevalent in the different NSCLC subtypes. © 2005 Wiley-Liss, Inc. [source]


Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer,

THE JOURNAL OF PATHOLOGY, Issue 4 2008
Y Tsukamoto
Abstract Genomic copy number aberrations (CNAs) are believed to play a major role in the development and progression of human cancers. Although many CNAs have been reported in gastric cancer, their genome-wide transcriptional consequences are poorly understood. In this study, to reveal the impact of CNAs on genome-wide expression in gastric cancer, we analysed 30 cases of gastric cancers for their CNAs by array comparative genomic hybridization (array CGH) and 24 of these 30 cases for their expression profiles by oligonucleotide-expression microarray. We found that with the application of laser microdissection, most CNAs were detected at higher frequency than in previous studies. Notably, gain at 20q13 was detected in almost all cases (97%), suggesting that this may play an important role in the pathogenesis of gastric cancer. By comparing the array CGH data with expression profiles of the same samples, we showed that both genomic amplification and deletion strongly influence the expression of genes in altered genomic regions. Furthermore, we identified 125 candidate genes, consisting of 114 up-regulated genes located in recurrent regions (>10%) of amplification and 11 down-regulated genes located in recurrent regions of deletion. Up-regulation of several candidate genes, such as CDC6, SEC61G, ANP32E, BYSL and FDFT1, was confirmed by immunohistochemistry. Interestingly, some candidate genes were localized at genomic loci adjacent to well-known genes such as EGFR, ERBB2 and SMAD4, and concordantly deregulated by genomic alterations. Based on these results, we propose that our list of candidate genes may contain novel genes involved in the pathogenesis of advanced gastric cancer. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]


DNA copy number alterations in prostate cancers: A combined analysis of published CGH studies

THE PROSTATE, Issue 7 2007
Jishan Sun
Abstract BACKGROUND Identifying genomic regions that are commonly deleted or gained in neoplastic cells is an important approach to identify tumor suppressor genes and oncogenes. Studies in the last two decades have identified a number of common DNA copy number alterations in prostate cancer. However, because of various sample sizes, diverse tumor types and sources, as well as a variety of detection methods with various sensitivities and resolutions, it is difficult to summarize and fully interpret the overall results. METHODS We performed a combined analysis of all published comparative genomic hybridization (CGH) studies of prostate cancer and estimated the frequency of alterations across the genome for all tumors, as well as in advanced and localized tumors separately. A total of 41 studies examining 872 cancers were included in this study. RESULTS The frequency of deletions and gains were estimated in all tumors, as well as in advanced and localized tumors. Eight deleted and five gained regions were found in more than 10% of the prostate tumors. An additional six regions were commonly deleted and seven were commonly gained in advanced tumors. While 8p was the most common location of deletion, occurring in about a third of all tumors and about half of advanced tumors, 8q was the most commonly gained region, affecting about a quarter of all tumors and about half of all advanced tumors. CONCLUSIONS The large number of tumors examined in this combined analysis provides better estimates of the frequency of specific alterations in the prostate cancer cell genome, and offers important clues for prioritizing efforts to identify tumor suppressor genes and oncogenes in these altered regions. Prostate 67: 692,700, 2007. © 2007 Wiley-Liss, Inc. [source]