CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas

Lifeng Sun, Angela A. Guzzetta, Tao Fu, Jinming Chen, Jana Jeschke, Ruby Kwak, Rajita Vatapalli, Stephen B. Baylin, Christine Iacobuzio-Donahue, Christopher L. Wolfgang, Nita Ahuja

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas.There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas.This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations.CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated).Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location.MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event.KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected.Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (nonwhite).These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance.

Original languageEnglish (US)
Pages (from-to)738-746
Number of pages9
JournalEpigenetics
Volume9
Issue number5
DOIs
StatePublished - Feb 11 2014
Externally publishedYes

Keywords

  • Ampullary adenomas
  • CpG island methylator phenotype
  • DNA methylation
  • Gastrointestinal tumors
  • Sporadic duodenal adenomas

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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  • Cite this

    Sun, L., Guzzetta, A. A., Fu, T., Chen, J., Jeschke, J., Kwak, R., Vatapalli, R., Baylin, S. B., Iacobuzio-Donahue, C., Wolfgang, C. L., & Ahuja, N. (2014). CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas. Epigenetics, 9(5), 738-746. https://doi.org/10.4161/epi.28082