Abstract 74: Genome-wide DNA methylation analysis of pT1a renal cell carcinoma and renal oncocytomas

Nephron sparing surgery (partial nephrectomy) is currently performed on small renal masses (4cm or less in size) confined to the kidney (pT1a). Up to 25% of small renal masses are benign, the majority being oncocytomas. Benign oncocytomas lack distinct radiographic findings on computerized tomography (CT) and cannot be diagnosed accurately using imaging alone. No difference in tumor size at presentation or tumor growth rate was noted between oncocytoma and RCC in a review of the literature. A needle biopsy or non-invasive urine based differential diagnosis of a benign lesion potentially would allow patients with equivocal renal lesions to avoid unnecessary surgery as well as anxiety if under active surveillance. The epigenetic alteration of aberrant DNA methylation has potential benefits as a choice of a biomarker because aberrant methylation occurs frequently and early in tumorgenesis and can be detected at extremely sensitive and specific levels by currently available technology. It is known that aberrant hypermethylation of the VHL gene occurs in a subset of clear cell RCC but is absent in oncocytoma. We hypothesized that additonal genes with a differential methylation status between benign oncocytoma and RCC could be identified. In this study, we performed genome-wide detection of DNA methylation in 25 RCC (pT1a), 25 oncocytomas of 4cm or less in size, and 4 age-matched histologically normal kidney tissues using the Infinium HumanMethylation27 BeadChip. To date, we have evidence that the profile of aberrant gene methylation is different between benign and malignant small renal masses matched for median size. Infinium-identified differentially methylated genes are validated using direct bisulfite sequencing, then a qMSP assay designed. If the panel of differentially methylated genes we have identified are verified in an independent set of small renal masses, we can then determine the predictive value of methylation-based detection of benign oncocytoma versus malignant RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 74. doi:10.1158/1538-7445.AM2011-74