Abstract 4716: Mitochondrial DNA variants in colorectal adenomatous polyps

Abstract Colorectal tumors mostly arise from sporadic adenomas (polyps). Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia and it has been well documented that polyps were benign tumors that may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types, with increasing malignant potential; tubular, tubulovillous, and villous. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, most efforts to identify genetic changes involved in adenomatous polyps have been focused on the nuclear genome. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (12 tubular and 5 matched surrounding normal tissues; 11 tubulovillous and 6 matched surrounding normal tissues and 14 villous and 9 matched surrounding normal tissues) obtained from the southern regional Cooperative Human Tissue Network (CHTN) and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs. Results from our data analyses revealed the presence of forty-seven variants in these mitochondrial genes; COX I, II, ATPase 6, 8, CYT b and ND 5. Six of the 49 variants detected were previously unreported and the MITODAT database [#J01415] was used as a sequence reference. Notably, a somatic variant C8515G/T in the MT-ATP 8 gene was observed at a frequency of 100% (12/12) in tubular adenomas and a germline variant 8327delA in the ATP 8 gene was observed at a frequency of 100% (47/47) among the tissue samples of the three adenomatous polyps. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (34/34) in tubular and villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, variant A9006G at MT-ATP 6 gene was observed at 74% (6/23) frequency of villous adenomas only. Interestingly, the A9006G variant was absent in six of the villous tissue samples that were clinicopathological designated as “polyvillous adenomas”. Our current data provide a basis for continued investigation of certain mtDNA variants as predictors of the three adenomatous polyps in a larger number of clinicopathological tissue specimens. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4716.