Molecular analysis of renal cell carcinoma with unclassfied histology [gene expression]

Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell RCC (nccRCC) that have no standard therapy. The oncogenic drivers in these tumors are unknown. We performed a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, Single Nucleotide Polymorphism array, fluorescence in-situ hybridization, immunohistochemistry, and cell-based assays. We identified recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%), and MTOR (8%). Integrated analysis revealed distinct molecular subsets, including a subset of 26% uRCC characterized by NF2-loss, dysregulated Hippo-YAP pathway and worse survival. Overall design: Analysis of RNA from uRCC with or without NF2-loss

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Chen YB, Xu J, Skanderup AJ, Dong Y, Brannon AR, Wang L, Won HH, Wang PI, Nanjangud GJ, Jungbluth AA, Li W, Ojeda V, Hakimi AA, Voss MH, Schultz N, Motzer RJ, Russo P, Cheng EH, Giancotti FG, Lee W, Berger MF, Tickoo SK, Reuter VE, Hsieh JJ