Epigenetic changes associated with neoplasms of the exocrine and endocrine pancreas

Mingzhou Guo, Yan Jia, Zhengtao Yu, Michael G. House, Manel Esteller, Malcolm V. Brock, James G. Herman

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Early detection and multi-modality curative treatment for pancreatic cancer remain unsatisfactory due to the insufficient understanding of the mechanisms underlying tumor progression. Epigenetic events, including aberrant methylation of tumor suppressor gene promoter regions, may contribute to tumorigenesis involving both the exocrine and endocrine pancreas. Methylation changes of specific gene promoter regions were examined in 48 resected neoplasms of the exocrine and endocrine pancreas, which were obtained as paraffin-embedded tissue samples. The pancreatic neoplasms included acinar cell carcinoma (n=12), adenocarcinoma (n=18), and islet cell tumors (n=18). DNA methylation was determined with a nested methylation-specific PCR (MSP) technique incorporating an initial bisulfite modification of tumor DNA for the promoter regions associated with 14 tumor suppressor genes. In decreasing order, the 6 most frequently methylated genes were: APC 50%, BRCA1 46%, p16INK4a 35%, p15INK4b 35%, RARβ 35%, and p73 33%. Overall, 94% of the tumors had methylation of at least one gene, and methylation of two or more genes was present in 69% of pancreatic tumors. Pancreatic adenocarcinomas had patterns of gene methylation that differed from pancreatic endocrine tumors. These differences were most notable for the APC and hMLH1 genes.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalDiscovery Medicine
Volume17
Issue number92
StatePublished - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Guo, M., Jia, Y., Yu, Z., House, M. G., Esteller, M., Brock, M. V., & Herman, J. G. (2014). Epigenetic changes associated with neoplasms of the exocrine and endocrine pancreas. Discovery Medicine, 17(92), 67-73.