A survey of tandem repeat instabilities and associated gene expression changes in 35 colorectal cancers

BMC Genomics

Research Article

Tugce Bilgin Sonay¹  Malamati Koletou²  Andreas Wagner³ 

[1] Anthropological Institute and Museum, University of Zurich, Zurich, Switzerland;Institute of Evolutionary Biology and Environmental Sciences, University of Zurich, Zurich, Switzerland;Department of Computer Science, ETH, Zurich, Switzerland;Institute of Evolutionary Biology and Environmental Sciences, University of Zurich, Zurich, Switzerland;The Swiss Institute of Bioinformatics, Lausanne, Switzerland;The Santa Fe Institute, Santa Fe, NM, United States of America;

关键词: Tandem repeats;    Colorectal cancer;    MSI;    Microsatellite instability;    Expression;    Repeat instability;    Microsatellite;    Cancer pathways;    Cancer genes;    Wnt signaling pathway;    p53 pathway;    Methylation;    Hypermetyhlation;   

DOI  :  10.1186/s12864-015-1902-9

 received in 2015-02-10, accepted in 2015-09-09,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundColorectal cancer is a major contributor to cancer morbidity and mortality. Tandem repeat instability and its effect on cancer phenotypes remain so far poorly studied on a genome-wide scale.ResultsHere we analyze the genomes of 35 colorectal tumors and their matched normal (healthy) tissues for two types of tandem repeat instability, de-novo repeat gain or loss and repeat copy number variation. Specifically, we study for the first time genome-wide repeat instability in the promoters and exons of 18,439 genes, and examine the association of repeat instability with genome-scale gene expression levels. We find that tumors with a microsatellite instable (MSI) phenotype are enriched in genes with repeat instability, and that tumor genomes have significantly more genes with repeat instability compared to healthy tissues. Genes in tumor genomes with repeat instability in their promoters are significantly less expressed and show slightly higher levels of methylation. Genes in well-studied cancer-associated signaling pathways also contain significantly more unstable repeats in tumor genomes. Genes with such unstable repeats in the tumor-suppressor p53 pathway have lower expression levels, whereas genes with repeat instability in the MAPK and Wnt signaling pathways are expressed at higher levels, consistent with the oncogenic role they play in cancer.ConclusionsOur results suggest that repeat instability in gene promoters and associated differential gene expression may play an important role in colorectal tumors, which is a first step towards the development of more effective molecular diagnostic approaches centered on repeat instability.

【 授权许可】

CC BY   
© Bilgin Sonay et al. 2015