Integrative genomics reveals mechanisms of copy number alterations responsible for transcriptional deregulation in colorectal cancer
- 18 August 2009
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 48 (11), 1002-1017
- https://doi.org/10.1002/gcc.20699
Abstract
To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array‐based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high‐level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations.Keywords
This publication has 43 references indexed in Scilit:
- Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profilingBlood, 2009
- Identification of Fat4 as a candidate tumor suppressor gene in breast cancersInternational Journal of Cancer, 2008
- The von Hippel-Lindau geneCancer, 2008
- The role of hormonal therapy in the management of hormonal-receptor-positive breast cancer with co-expression of HER2Nature Clinical Practice Oncology, 2008
- Characterization of amplicons in neuroblastoma: High‐resolution mapping using DNA microarrays, relationship with outcome, and identification of overexpressed genesGenes, Chromosomes and Cancer, 2008
- Cancer Statistics, 2008CA: A Cancer Journal for Clinicians, 2008
- Characterization of a cryptic 3.3 Mb deletion in a patient with a “balanced t(15;22) translocation” using high density oligo array CGH and gene expression arraysAmerican Journal of Medical Genetics Part A, 2008
- Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancerProceedings of the National Academy of Sciences of the United States of America, 2007
- Bystin in human cancer cells: intracellular localization and function in ribosome biogenesisBiochemical Journal, 2007
- A collection of breast cancer cell lines for the study of functionally distinct cancer subtypesCancer Cell, 2006