Genomic Characterization of Renal Cell Carcinoma with Sarcomatoid Dedifferentiation Pinpoints Recurrent Genomic Alterations

European Urology
Gabriel G MaloufJose A Karam

Abstract

The genomic features underpinning renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) are not well understood, and at present, there are no specific or effective therapies for sRCC. To identify genomic alterations in patients with sRCC. We conducted genomic profiling on paired epithelial and sarcomatoid areas of three sRCC cases. Genomic profiling was performed on another 23 sRCC patients harboring diverse epithelial components (total of 26 cases). Genomic profiling was conducted using a hybrid capture DNA next-generation sequencing assay of 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Results were compared with 56 similarly sequenced cases of clear cell RCC (ccRCC) devoid of a sarcomatoid component, and with clear cell, papillary, and chromophobe renal cell carcinoma datasets from The Cancer Genome Atlas. Four additional ccRCC cases underwent whole exome sequencing. Genomic alterations in patients with sRCC and ccRCC were described, and their frequencies were compared using the Fisher exact test. Two of three patients with sRCC who underwent genomic profiling of both their epithelial and sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated common...Continue Reading

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