Instabilotyping: Comprehensive identification of frameshift mutations caused by coding region microsatellite instability

Yuriko Mori, Jing Yin, Asma Rashid, Barbara A. Leggett, Joanne Young, Lisa Simms, Peter M. Kuehl, Patricia Langenberg, Stephen J. Meltzer, O. Colin Stine

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Coding region frameshift mutation caused by microsatellite instability (MSI) is one mechanism contributing to tumorigenesis in cancers with MSI in high frequency. Mutation of TGFBR2 is one example of this process. To identify additional examples, a large-scale genomic screen of coding region microsatellites was conducted. 1115 coding homopolymeric loci with six or more nucleotides were identified in an online genetic database. Mutational screening was performed at 152 of these loci in 46 colorectal tumors with MSI in high frequency. Nine loci were mutated in ≥20% of tumors, 10 loci in 10-20%, 24 loci in 5-10%, 43 loci in <5%, and 66 loci were not mutated in any tumors. The most frequently mutated novel loci were the activin type II receptor gene (58.1%), SEC63 (48.8%), AIM 2 (47.6%), a gene encoding a subunit of the NADH-ubiquinone oxidoreductase complex (27.9%), a homologue of mouse cordon-bleu (23.8%), and EBPI/PA2G4 (20.9%). This genome-wide approach identifies coding region MSI in genes or pathways not implicated previously in colorectal tumorigenesis, which may merit functional study or other additional analysis.

Original languageEnglish (US)
Pages (from-to)6046-6049
Number of pages4
JournalCancer Research
Volume61
Issue number16
StatePublished - Aug 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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