Relationship of gene expression and chromosomal abnormalities in colorectal cancer Journal Article
| Authors: | Tsafrir, D.; Bacolod, M.; Selvanayagam, Z.; Tsafrir, I.; Shia, J.; Zeng, Z.; Liu, H.; Krier, C.; Stengel, R. F.; Barany, F.; Gerald, W. L.; Paty, P. B.; Domany, E.; Notterman, D. A. |
| Article Title: | Relationship of gene expression and chromosomal abnormalities in colorectal cancer |
| 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. ©2006 American Association for Cancer Research. |
| Keywords: | single nucleotide polymorphism; cancer growth; liver neoplasms; neoplasm staging; colorectal cancer; metastasis; gene expression; gene expression profiling; lung neoplasms; genetic transcription; colorectal neoplasms; chromosome aberration; adenoma; colon cancer; carcinogenicity; dna, neoplasm; carcinoma; dna microarray; chromosome 8p; chromosome aberrations; gene dosage; comparative genomic hybridization; chromosome 18; dna transcription; gene location; cell selection; chromosome 14q; chromosome 1p; chromosome 20q; chromosome 7p; chromosome 8q; chromosome 15q; colon adenoma; chromosome 13q; chromosomes, human, pair 20; chromosome 4; chromosome 5q; dna content |
| Journal Title: | Cancer Research |
| Volume: | 66 |
| Issue: | 4 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2006-02-15 |
| Start Page: | 2129 |
| End Page: | 2137 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-05-2569 |
| PUBMED: | 16489013 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 113" - "Export Date: 4 June 2012" - "CODEN: CNREA" - "Source: Scopus" |
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