POLYBROM0-1 MUTATIONS IN CLEAR CELL RENAL CELL CARCINOMA TUMORS FROM PATIENTS IN EASTERN EUROPE

Abstract

There were approximately 65,000 cases of renal cancer worldwide in 2012, the majority being sporadic clear cell renal cell carcinoma (ccRCC). Nearly all patients who progress to metastatic ccRCC will succumb to the disease. Improved molecular characterization of ccRCC is necessary to improve patient outcomes. Recent studies have shown the gene PRIM1 to be frequently mutated in ccRCC. In this study, we confirm PBRM1 as an important gene in ccRCC, somatically mutated in 40% of tumors from an Eastern European cohort. We also demonstrate an efficient screening method combining traditional Sanger sequencing, next-generation ion Torrent sequencing, and targeted data analysis. Finally, we use Affymetrix gene expression analysis of ccRCC tumor RNA to identify several candidate genes, including FosB, SLC5A1, and SLC34A2, and signaling pathways involved in hormonal regulation and kidney development, among others, which are affected by PBRM1 mutation and which merit further study as novel therapeutic inhibitors in PBRM1-mutant ccRCC.