Document Detail


Integrated analysis of genome-wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype-negative colon cancer.
MedLine Citation:
PMID:  23341073     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microsatellite stable (MSS), CpG island methylator phenotype (CIMP)-negative colorectal tumors, the most prevalent molecular subtype of colorectal cancer, are associated with extensive copy number alteration (CNA) events and aneuploidy. We report on the identification of characteristic recurrent CNA (with frequency >25%) events and associated gene expression profiles for a total of 40 paired tumor and adjacent normal colon tissues using genome-wide microarrays. We observed recurrent CNAs, namely gains at 1q, 7p, 7q, 8p12-11, 8q, 12p13, 13q, 20p, 20q, Xp, and Xq and losses at 1p36, 1p31, 1p21, 4p15-12, 4q12-35, 5q21-22, 6q26, 8p, 14q, 15q11-12, 17p, 18p, 18q, 21q21-22, and 22q. Within these genomic regions we identified 356 genes with significant differential expression (P < 0.0001 and ±1.5-fold change) in the tumor compared to adjacent normal tissue. Gene ontology and pathway analyses indicated that many of these genes were involved in functional mechanisms that regulate cell cycle, cell death, and metabolism. An amplicon present in >70% of the tumor samples at 20q11-20q13 contained several cancer-related genes (AHCY, POFUT1, RPN2, TH1L, and PRPF6) that were upregulated and demonstrated a significant linear correlation (P < 0.05) for gene dosage and gene expression. Copy number loss at 8p, a CNA associated with adenocarcinoma and poor prognosis, was observed in >50% of the tumor samples and demonstrated a significant linear correlation for gene dosage and gene expression for two potential tumor suppressor genes, MTUS1 (8p22) and PPP2CB (8p12). The results from our integration analysis illustrate the complex relationship between genomic alterations and gene expression in colon cancer.
Authors:
Lenora W M Loo; Maarit Tiirikainen; Iona Cheng; Annette Lum-Jones; Ann Seifried; James M Church; Robert Gryfe; Daniel J Weisenberger; Noralane M Lindor; Steven Gallinger; Robert W Haile; David J Duggan; Stephen N Thibodeau; Graham Casey; Loïc Le Marchand
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-23
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  52     ISSN:  1098-2264     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-03-15     Completed Date:  2013-08-26     Revised Date:  2014-05-14    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  450-66     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Adenoma / genetics*,  metabolism
Allelic Imbalance
Carcinoma / genetics*,  metabolism
Colonic Neoplasms / genetics*,  metabolism
CpG Islands*
DNA Copy Number Variations*
DNA Methylation
Gene Expression
Gene Expression Regulation, Neoplastic*
Genome-Wide Association Study
Humans
Microsatellite Instability
Microsatellite Repeats
Oligonucleotide Array Sequence Analysis
Phenotype
Transcriptome
Grant Support
ID/Acronym/Agency:
5U24 CA074806/CA/NCI NIH HHS; CA-95-011/CA/NCI NIH HHS; U01 CA074783/CA/NCI NIH HHS; U01 CA074783/CA/NCI NIH HHS; U01 CA074799/CA/NCI NIH HHS; U01 CA074799/CA/NCI NIH HHS; U01 CA074800/CA/NCI NIH HHS; U01 CA074800/CA/NCI NIH HHS; U01 CA074806/CA/NCI NIH HHS; U01 CA074806/CA/NCI NIH HHS; U24 CA074783/CA/NCI NIH HHS; U24 CA074799/CA/NCI NIH HHS; U24 CA074800/CA/NCI NIH HHS; U24 CA074806/CA/NCI NIH HHS; U24 CA097735/CA/NCI NIH HHS
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