Contrasting Features of Papillary and Chromophobe Renal Cell Carcinoma Revealed by Whole-Genome Sequencing.

UNLABELLED: The identification of cancer drivers is a cornerstone to the delivery of precision oncology. So far, sequencing of renal cell cancer (RCC) has largely been confined to the clear cell subtype of RCC. In contrast, sequencing analyses of the less common forms of RCC, papillary RCC (pRCC) and chromophobe RCC (ChRCC), have so far been limited. We analyzed whole-genome sequencing data on 164 tumor-normal pairs from the Genomics England 100,000 Genomes Project, providing a comprehensive, high-resolution map of copy number alterations, structural variation, and key global genomic features, including mutational signatures, intratumor heterogeneity, and analysis of extrachromosomal DNA formation. Our research establishes correlations between genomic alterations and histologic diversification and the extent to which genetically-mediated immune escape contributes to the development of these RCC subtypes.

IMPLICATIONS: We demonstrate the distinctive genetics that characterizes pRCC and ChRCC and how this information has the potential to inform patient treatment and clinical trials.