Relationship of Gene Expression and Chromosomal Abnormalities in Colorectal Cancer Export

@article{citeulike:1239823, abstract = {Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and gene expression have not been adequately explored nor globally monitored during the progression of the disease. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the disease. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are correlated with alterations in DNA content. Often, large chromosomal segments, containing multiple genes, are transcriptionally affected in a coordinated way, and we show that the underlying mechanism is a corresponding change in DNA content. This implies that whereas specific chromosomal abnormalities may arise stochastically, the associated changes in expression of some or all of the affected genes are responsible for selecting cells bearing these abnormalities for clonal expansion. Indeed, particular chromosomal regions are frequently gained and overexpressed (e.g., 7p, 8q, 13q, and 20q) or lost and underexpressed (e.g., 1p, 4, 5q, 8p, 14q, 15q, and 18) in primary colon tumors, making it likely that these changes favor tumorigenicity. Furthermore, we show that these aberrations are absent in normal colon mucosa, appear in benign adenomas (albeit only in a small fraction of the samples), become more frequent as disease advances, and are found in the majority of metastatic samples. (Cancer Res 2006; 66(4): 2129-37) 10.1158/0008-5472.CAN-05-2569}, author = {Tsafrir, Dafna and Bacolod, Manny and Selvanayagam, Zachariah and Tsafrir, Ilan and Shia, Jinru and Zeng, Zhaoshi and Liu, Hao and Krier, Curtis and Stengel, Robert F. and Barany, Francis and Gerald, William L. and Paty, Philip B. and Domany, Eytan and Notterman, Daniel A.}, citeulike-article-id = {1239823}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-05-2569}, citeulike-linkout-1 = {http://cancerres.aacrjournals.org/cgi/content/abstract/66/4/2129}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16489013}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16489013}, day = {15}, doi = {10.1158/0008-5472.CAN-05-2569}, journal = {Cancer Res}, keywords = {array-cgh, colon\_cancer, crc\_bib, gene\_expression, integration, progression, snp-arrays}, month = {February}, number = {4}, pages = {2129--2137}, posted-at = {2008-02-11 12:17:14}, priority = {0}, title = {Relationship of Gene Expression and Chromosomal Abnormalities in Colorectal Cancer}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-05-2569}, volume = {66}, year = {2006} }

TY - JOUR ID - citeulike:1239823 L3 - citeulike-article-id:1239823 N2 - Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and gene expression have not been adequately explored nor globally monitored during the progression of the disease. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the disease. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are correlated with alterations in DNA content. Often, large chromosomal segments, containing multiple genes, are transcriptionally affected in a coordinated way, and we show that the underlying mechanism is a corresponding change in DNA content. This implies that whereas specific chromosomal abnormalities may arise stochastically, the associated changes in expression of some or all of the affected genes are responsible for selecting cells bearing these abnormalities for clonal expansion. Indeed, particular chromosomal regions are frequently gained and overexpressed (e.g., 7p, 8q, 13q, and 20q) or lost and underexpressed (e.g., 1p, 4, 5q, 8p, 14q, 15q, and 18) in primary colon tumors, making it likely that these changes favor tumorigenicity. Furthermore, we show that these aberrations are absent in normal colon mucosa, appear in benign adenomas (albeit only in a small fraction of the samples), become more frequent as disease advances, and are found in the majority of metastatic samples. (Cancer Res 2006; 66(4): 2129-37) 10.1158/0008-5472.CAN-05-2569 IS - 4 JF - Cancer Res EP - 2137 TI - Relationship of Gene Expression and Chromosomal Abnormalities in Colorectal Cancer VL - 66 SP - 2129 KW - array-cgh KW - colon_cancer KW - crc_bib KW - gene_expression KW - integration KW - progression KW - snp-arrays AU - Tsafrir, Dafna AU - Bacolod, Manny AU - Selvanayagam, Zachariah AU - Tsafrir, Ilan AU - Shia, Jinru AU - Zeng, Zhaoshi AU - Liu, Hao AU - Krier, Curtis AU - Stengel, Robert AU - Barany, Francis AU - Gerald, William AU - Paty, Philip AU - Domany, Eytan AU - Notterman, Daniel PY - 2006/02/15/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-05-2569 ER -