Identification of chromosomal copy number variations and novel candidate loci in hereditary nonpolyposis colorectal cancer with mismatch repair proficiency.

Identification of chromosomal copy number variations and novel candidate loci in hereditary nonpolyposis colorectal cancer with mismatch repair proficiency.
Genomics. 2013 Feb 20;
Authors: Chen W, Yuan L, Cai Y, Chen X, Chi Y, Wei P, Zhou X, Shi D
Abstract
The pathogenesis of microsatellite stable hereditary non-polyposis colorectal cancers (MSS HNPCC) is unclear. To identify genomic regions that might be involved in MSS HNPCC pathogenesis, we selected 20 pairs of MSS HNPCC for a genome-wide study using copy number variation targeted (CNV-targeted) CytoScan HD Array. A remarkably increased frequency of 20q gain (70%) and high levels of copy-neutral loss of heterozygosity (40%) were observed. The most frequent tumor-specific CNVs included amplifications (7p21.3-15.1, 8q13.3-24.3, 13q14.1-33.3 and 20q12-13.33) and deletions (8p11.23-23.1, 15q11.2-26.1, 17p13.1-13.3 and 18q11.2-21.33). In addition, 10 novel CNVs were discovered and led to identification of WDR16 and RAPGEF5 as candidate genes involved in tumorigenesis, displaying a robust correlation between expression and genomic alterations. Moreover, WDR16 and RAPGEF5 exhibited altered protein expression levels as assessed by immunohistochemistry (IHC) in 41 other independent samples. Finally, high consistencies (68-84%) were observed between CNVs by Array and quantitative PCR. These findings are important for further elucidating MSS HNPCC pathogenesis.
PMID: 23434627 [PubMed - as supp...

Source: Genomics - February 20, 2013 Category: Genetics & Stem Cells Authors: Chen W, Yuan L, Cai Y, Chen X, Chi Y, Wei P, Zhou X, Shi D Tags: Genomics Source Type: research