RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas

David Shibata, Yuriko Mori, Kun Cai, Li Zhang, Jing Yin, Abul Elahi, Richard Hamelin, Yick F. Wong, Wing K. Lo, Tony K H Chung, Fumiaki Sato, Martin S. Karpeh, Stephen Meltzer

Research output: Contribution to journalArticle

Abstract

The recently described gene, RAB32, is a ras proto-oncogene family member that encodes an A-kinase-anchoring protein. RAB32 has been found to be frequently hypermethylated in microsatellite instability-high (MSI-H) colon cancers. We sought to determine the prevalence of RAB32 hypermethylation in gastric and endometrial adenocarcinomas, the 2 other major tumor types in which MSI-H is common. Moreover, we delineated the association of RAB32 hypermethylation with microsatellite instability (MSI) and hMLH1 hypermethylation. MSI status and hypermethylation of the RAB32 and hMLH1 genes were studied in paired primary normal and tumor tissues from 48 patients with gastric cancer. An additional 80 endometrial cancer patients were studied for RAB32 methylation and MSI status. Thirteen (27%) of 48 gastric cancers demonstrated evidence of RAB32 hypermethylation. MSI status was determined in 46 of the tumors, with 7 (100%) of 7 MSI-H tumors, 1 (33%) of 3 MSI-low (MSI-L) tumors and 4 (11%) of 36 microsatellite-stable (MSS) tumors found to harbor RAB32 hypermethylation. RAB32 methylation was significantly associated with intestinal type histology and concomitant hMLH1 hypermethylation in gastric cancer. In contrast, RAB32 methylation occurred in only 1 of 80 endometrial cancers, including 20 MSI-H, 8 MSI-L and 52 MSS tumors. Hypermethylation of hMLH1 was noted in 16 (20%) of 80 endometrial tumors. We conclude that although RAB32 methylation is rare in endometrial cancers, it is strongly associated with hMLH1 hypermethylation and MSI in gastric adenocarcinomas. Given its similar involvement in colon cancer, RAB32 inactivation may represent a component of the oncogenic pathway of microsatellite-unstable gastrointestinal adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)801-806
Number of pages6
JournalInternational Journal of Cancer
Volume119
Issue number4
DOIs
Publication statusPublished - Aug 15 2006
Externally publishedYes

    Fingerprint

Keywords

  • Endometrial cancer
  • Gastric cancer
  • Methylation
  • Microsatellite instability
  • RAB32

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this