Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers

Yuriko Mori, Fumiaki Sato, Florin M. Selaru, Andreea Olaru, Kellie Perry, Martha C. Kimos, Gen Tamura, Nagahide Matsubara, Suna Wang, Yan Xu, Jing Yin, Tong Tong Zou, Barbara Leggett, Joanne Young, Toshihiro Nukiwa, O. Colin Stine, John M. Abraham, David Shibata, Stephen J. Meltzer

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Microsatellite instability (MSI) within coding regions causes frameshift mutations (FSMs). This type of mutation may inactivate tumor suppressor genes in cancers with frequent MSI (MSI-H cancers). To identify novel FSMs in gastric carcinogenesis in an unbiased and comprehensive manner, we screened for this type of mutation at 154 coding region repeat loci in 18 MSI-H gastric cancers. We also compared FSM rates and spectra in MSI-H gastric versus colorectal cancers. Thirteen novel loci showed FSMs in >20% of gastric tumors. Novel loci with the highest mutation frequencies included the activin type 2 receptor gene (44.4%), DKFZp564K112 (a homologue of the Drosophila tumor suppressor gene multi-sex-combs; 41.2%), and an endoplasmic reticulum chaperone protein gene SEC63 (37.5%). The mutational spectra for genes with high mutation frequencies were also significantly different between MSI-H gastric and colorectal cancers.

Original languageEnglish (US)
Pages (from-to)3641-3645
Number of pages5
JournalCancer Research
Volume62
Issue number13
StatePublished - Jul 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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