Location of Repository

3'UTR poly(T/U) tract deletions and altered expression of EWSR1 are a hallmark of mismatch repair deficient cancers

By Shivendra Kishore, Salvatore Piscuoglio, Michal Kovac, Annette Gylling, Friedel Wenzel, Francesca Trapani, Hans Joerg Altermatt, Valentina Mele, Giancarlo Marra, Päivi Peltomäki, Luigi Terracciano, Mihaela Zavolan and Karl Heinimann

Abstract

The genome-wide accumulation of DNA replication errors known as microsatellite instability (MSI) is the hallmark lesion of DNA mismatch repair (MMR) deficient cancers. Although testing for MSI is widely used to guide clinical management, the contribution of MSI at distinct genic loci to the phenotype remains largely unexplored. Here we report that a mononucleotide (T/U)16 tract located in the 3' untranslated region (3'UTR) of the Ewing sarcoma breakpoint region 1 (EWSR1) gene is a novel MSI target locus that shows perfect sensitivity and specificity in detecting mismatch-repair deficient cancers in two independent populations. We further found a striking re-localization of the EWSR1 protein from nucleus to cytoplasm in MMR-deficient cancers, and that the non-protein coding MSI target locus itself has a modulatory effect on EWSR1 gene expression through alternative 3' end processing of the EWSR1 gene. Our results point to a MSI target gene-specific effect in MMR-deficient cancers

Publisher: American Association for Cancer Research
Year: 2014
DOI identifier: 10.1158/0008-5472.CAN-13-2100
OAI identifier: oai:edoc.unibas.ch:31693
Provided by: edoc
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://edoc.unibas.ch/dok/A619... (external link)
  • https://edoc.unibas.ch/31693/ (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.