title: A survey of tandem repeat instabilities and associated gene expression changes in 35 colorectal cancers.
abstract: BACKGROUND
  Colorectal 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.
  
  
  RESULTS
  Here 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Anthropological Institute and Museum, University of Zurich, Zurich, Switzerland. tugce.bilgin@uzh.ch.|Institute of Evolutionary Biology and Environmental Sciences, University of Zurich, Zurich, Switzerland. tugce.bilgin@uzh.ch.
authors.forename: Tugce Bilgin
authors.initials: TB
authors.lastname: Sonay
authors.affiliation: Department of Computer Science, ETH, Zurich, Switzerland. koletoum@student.ethz.ch.
authors.forename: Malamati
authors.initials: M
authors.lastname: Koletou
authors.affiliation: Institute of Evolutionary Biology and Environmental Sciences, University of Zurich, Zurich, Switzerland. andreas.wagner@ieu.uzh.ch.|The Swiss Institute of Bioinformatics, Lausanne, Switzerland. andreas.wagner@ieu.uzh.ch.|The Santa Fe Institute, Santa Fe, NM, United States of America. andreas.wagner@ieu.uzh.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wagner
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D042822:Genomic Instability; D006801:Humans; D053842:Microsatellite Instability; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D020080:Tandem Repeat Sequences; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53