537 Background: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is found in five percent of all renal cell carcinoma (RCC) cases, and has a significantly worse prognosis relative to matched highgrade RCC with only epithelial elements. The genomic features underpinning sRCC are not well understood, and at present, there are no specific or effective therapies for sRCC. Methods: We conducted comprehensive genomic profiling (CGP) on paired epithelial and sarcomatoid areas of 3 sRCC cases. In the course of routine clinical care, CGP was performed on another 23 sRCC harboring diverse epithelial components. CGP was conducted using a hybrid capture next generation DNA sequencing assay(NGS) of 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Results were compared with 56 similarly sequenced cases of clear cell RCC devoid of sarcomatoid component, and with clear cell TCGA. Results: Two of three sRCC cases that underwent CGP of both their epithelial and the sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 23 sRCC, TP53(43%), CDKN2A(30%), VHL(26%) and NF2(22%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations. Conclusions: Two of three sRCC cases that underwent CGP of both their epithelial and the sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 23 sRCC, TP53(43%), CDKN2A(30%), VHL(26%) and NF2(22%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations.
690P Comprehensive genomic profiling (CGP) of VHL mutated and VHL wild type clear cell renal cell carcinoma (ccRCC)
