The genomics of renal cell carcinoma and its role in renal mass biopsy.

Abstract

Large-scale genomic profiling has shed new light on the molecular underpinnings of renal cell carcinoma (RCC), spurring a much needed refinement of RCC subclassification based on an integrative assessment of histopathologic features and molecular alterations. At the same time, renal mass biopsies have become increasingly commonplace, necessitating ancillary tools to help guide clinical management. Herein, we briefly review our current understanding of RCC genomics, highlighting areas of possible clinical utility, as well as potential limitations, for renal mass biopsies. Distinct RCC subtypes harbor characteristic molecular features, including somatic mutations, copy number alterations, and genomic rearrangements. Existing ancillary tools, including fluorescent in-situ hybridization and immunohistochemistry, may be useful for diagnostic subclassification. Recurrent secondary molecular alterations in clear cell RCC (BAP1, SETD2, PBRM1, and TP53) and papillary RCC (CDKN2A) may be associated with poor prognosis; however, intratumoral genomic heterogeneity may limit the clinical utility of these molecular biomarkers in renal mass biopsies. Recent technological advances have the potential to fundamentally alter the clinical management of RCC by leveraging our increasing understanding of RCC genomics to assess hundreds of molecular biomarkers simultaneously. Additional focused molecular analyses of renal mass biopsy cohorts are needed prior to widespread implementation of molecular biomarker assays.