MP23-08 MICRORNA-29S INHIBITS CANCER CELL MIGRATION AND INVASION VIA TARGETING FOCAL ADHESION PATHWAYS IN RENAL CELL CARCINOMA

single site biopsies in renal cell carcinoma (RCC). We sought to characterize the extent of clonal branching present in distinct regions of primary renal tumors. METHODS: Ex vivo core needle biopsies were obtained from three to four geographically distinct regions of renal tumors that were resected via partial or radical nephrectomy at a single institution from 10/2012 to 6/2013. DNA was extracted and subjected to next-generation sequencing, focusing on the coding regions for nine genes with known associations to renal cell carcinoma (VHL, PBRM1, SETD2, BAP1, KDM5C, MTOR, PIK3CA, EGFR, PTEN). We then constructed phylogenetic trees for each tumor by inferring clonal evolution based on mutations present within each core. RESULTS: We obtained 45 biopsy cores from 14 patients with clear cell histology RCC (median tumor size 4.5 cm, interquartile range 4.0 e 5.9 cm). A total of 9/14 tumors (64%) were grade 3 and 6/14 (43%) were stage 3. The mutation rates for each studied gene are represented in Figure 1. Four patients (29%) had no detectable mutations and three patients (21%) had a single mutation. Branching patterns of various complexities were observed in patients with two or more mutations (example: Figure 2). When VHL mutations were present, they were identical and occurred ubiquitously in all core samples, likely reflecting an early event in tumorigenesis. In contrast, when KDM5C mutations were present they were only detected in one or two cores, an example of regional mutational diversity. When SETD2, PBRM1, and BAP1 mutations were present, they were present in all cores 50%, 50%, and 25% of the time, respectively. CONCLUSIONS: Ex vivo core needle biopsies reveal regional variations in gene mutations associated with clear cell RCC. Single site needle biopsy assessment of diagnostic or prognostic genetic mutations is unlikely to reflect the broader tumor landscape. This presents a challenge in the validation of biomarkers when utilizing a single core biopsy. Source of Funding: Sidney Kimmel Center for Prostate and Urologic Cancers