MP47-04 EXAMINATION OF GENOMIC COPY NUMBER ALTERATIONS IN RENAL CELL CARCINOMA WITH SARCOMATOID FEATURES (2015)

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2015MP47-04 EXAMINATION OF GENOMIC COPY NUMBER ALTERATIONS IN RENAL CELL CARCINOMA WITH SARCOMATOID FEATURES Timothy Ito, Jianming Pei, Essel Dulaimi, Craig Menges, Philip Abbosh, Marc Smaldone, David Chen, Richard Greenberg, Alexander Kutikov, Rosalia Viterbo, Robert Uzzo, and Joseph Testa Timothy ItoTimothy Ito More articles by this author , Jianming PeiJianming Pei More articles by this author , Essel DulaimiEssel Dulaimi More articles by this author , Craig MengesCraig Menges More articles by this author , Philip AbboshPhilip Abbosh More articles by this author , Marc SmaldoneMarc Smaldone More articles by this author , David ChenDavid Chen More articles by this author , Richard GreenbergRichard Greenberg More articles by this author , Alexander KutikovAlexander Kutikov More articles by this author , Rosalia ViterboRosalia Viterbo More articles by this author , Robert UzzoRobert Uzzo More articles by this author , and Joseph TestaJoseph Testa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1524AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sarcomatoid differentiation is an uncommon histological finding in renal cell carcinoma (RCC) that may develop from any RCC subtype and is associated with a very poor prognosis. The identification of genetic alterations that drive this aggressive phenotype could aid in the development of more effective targeted therapies. In this study, we aimed to identify unique copy number alterations in patients with sarcomatoid RCC when compared to those with other RCC subtypes. METHODS Genomic copy number analysis was performed using single nucleotide polymorphism (SNP)-based microarrays on tissue extracted from the tumors of 80 patients (9 with sarcomatoid features (sRCC), 39 clear cell (ccRCC), 26 papillary (pRCC) and 6 chromophobe RCC (chRCC)) who underwent renal mass excision between 2010 - 2014. Statistical analysis was performed using Kaplan Meier (KM) survival analysis, t-tests and Fisher exact tests where appropriate. RESULTS sRCC tumors exhibited significantly higher numbers of copy number alterations when compared to ccRCC, pRCC and chRCC (mean 20.1 vs. 6.6 vs. 7.0 vs. 6.3, respectively; p <0.0001). The most common copy number losses occurred in chromosome arms 1p, 3p, 9q, 13q, 14, 15q, 18q, 21q, and 22q. Among these, the copy number losses occurring at a significantly higher frequency among sRCC tumors when compared to the other 3 histologies included 9q (88% vs 14%, p<0.0001), 15q (77% vs 4%, p<0.0001), 18q (66% vs 14%, p=0.002), and 22q (77 vs 10%, p<0.0001). The most common copy number gains were in chromosome arms 1q, 8q, 17q, and 20p/q, with 1q (55% vs 4%, p=0.0003) and 8q (66% vs 3%, p<0.0001) gains occurring at a significantly higher frequency when compared to the other 3 histologies. Of the sRCC tumors, 3 arose from ccRCC, 2 from pRCC and 4 from unclassified RCC. sRCC was associated with worse survival compared to ccRCC, pRCC and chRCC as assessed by KM analysis (p=0.0006), and higher rates of lymph node positivity (77% vs. 3% vs. 12% vs. 0%, respectively; p<0.0001) and metastases (100% vs. 13% vs. 4% vs. 0%, respectively; p<0.0001) on presentation were observed in sRCC. CONCLUSIONS Sarcomatoid differentiation in RCC is associated with a high rate of chromosomal imbalances with unique copy number alterations including losses of 9q, 15q, 18q and 22q and gains of 1q and 8q. Identification and validation of candidate driver genes or tumor suppressor loci within these chromosomal regions may help identify targets for future therapies. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e553 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Timothy Ito More articles by this author Jianming Pei More articles by this author Essel Dulaimi More articles by this author Craig Menges More articles by this author Philip Abbosh More articles by this author Marc Smaldone More articles by this author David Chen More articles by this author Richard Greenberg More articles by this author Alexander Kutikov More articles by this author Rosalia Viterbo More articles by this author Robert Uzzo More articles by this author Joseph Testa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...