Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma

BMC Genomics

Research Article

Alisa M Goldstein¹  Nan Hu¹  Philip R Taylor¹  Chaoyu Wang¹  Robert J Clifford²  Maxwell P Lee²  Howard H Yang²  Ti Ding³ 

[1] Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA;Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, NIH, DHHS, BethesdaMaryland, USA;Shanxi Cancer Hospital, 030013, Taiyuan, Shanxi, PR China;

关键词: Esophageal Squamous Cell Carcinoma;    Copy Number Alteration;    Esophageal Squamous Cell Carcinoma Patient;    Copy Number Gain;    Copy Number Loss;   

DOI  :  10.1186/1471-2164-11-576

 received in 2010-02-28, accepted in 2010-10-18,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGenomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors using the Affymetrix GeneChip Human Mapping 500K array in 30 cases from a high-risk region of China. In the current study we focused on copy number neutral (CN = 2) LOH (CNNLOH) and its relation to gene expression in ESCC.ResultsOverall we found that 70% of all LOH observed was CNNLOH. Ninety percent of ESCCs showed CNNLOH (median frequency in cases = 60%) and this was the most common type of LOH in two-thirds of cases. CNNLOH occurred on all 39 autosomal chromosome arms, with highest frequencies on 19p (100%), 5p (96%), 2p (95%), and 20q (95%). In contrast, LOH with CN loss represented 19% of all LOH, occurred in just half of ESCCs (median frequency in cases = 0%), and was most frequent on 3p (56%), 5q (47%), and 21q (41%). LOH with CN gain was 11% of all LOH, occurred in 93% of ESCCs (median frequency in cases = 13%), and was most common on 20p (82%), 8q (74%), and 3q (42%). To examine the effect of genomic instability on gene expression, we evaluated RNA profiles from 17 pairs of matched normal and tumor samples (a subset of the 30 ESCCs) using Affymetrix U133A 2.0 arrays. In CN neutral regions, expression of 168 genes (containing 1976 SNPs) differed significantly in tumors with LOH versus tumors without LOH, including 101 genes that were up-regulated and 67 that were down-regulated.ConclusionOur results indicate that CNNLOH has a profound impact on gene expression in ESCC, which in turn may affect tumor development.

【 授权许可】

Unknown   
© Hu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.