MP23-07 REGIONAL GENETIC VARIABILITY DETECTED WITH RENAL TUMOR BIOPSIES: IMPLICATIONS IN BIOMARKER DEVELOPMENT (2014)

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2014MP23-07 REGIONAL GENETIC VARIABILITY DETECTED WITH RENAL TUMOR BIOPSIES: IMPLICATIONS IN BIOMARKER DEVELOPMENT Alexander Sankin, Nina Mikkilineni, A. Ari Hakimi, Mikhail Silk, Yupu Liang, Roy Mano, Jeremy C. Durack, Jonathan Coleman, Paul Russo, and James Hsieh Alexander SankinAlexander Sankin More articles by this author , Nina MikkilineniNina Mikkilineni More articles by this author , A. Ari HakimiA. Ari Hakimi More articles by this author , Mikhail SilkMikhail Silk More articles by this author , Yupu LiangYupu Liang More articles by this author , Roy ManoRoy Mano More articles by this author , Jeremy C. DurackJeremy C. Durack More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , Paul RussoPaul Russo More articles by this author , and James HsiehJames Hsieh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.875AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intratumor heterogeneity can lead to an underestimation of the genetic landscape detected from 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 – 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. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e244-e245 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Alexander Sankin More articles by this author Nina Mikkilineni More articles by this author A. Ari Hakimi More articles by this author Mikhail Silk More articles by this author Yupu Liang More articles by this author Roy Mano More articles by this author Jeremy C. Durack More articles by this author Jonathan Coleman More articles by this author Paul Russo More articles by this author James Hsieh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...