Precision medicine from the renal cancer genome

Abstract

Genomics is revolutionizing our understanding of the molecular basis of renal cell carcinoma (RCC). The advent of unbiased genome-wide association studies has led to the discovery of previously unrecognized genetic predisposing factors that impact an individual's risk of developing RCC. Moreover, large-scale investigations of somatic alterations of the genomic and transcriptomic landscapes in tumours using next-generation sequencing technology have revealed new information on the molecular pathways that are characteristically disrupted in various RCC subtypes. Sequencing studies have revealed that epigenetic machinery and chromatin remodelling complexes are disrupted in >80% of clear cell RCC tumours, the most common form of the disease. The growing knowledge of subtype-specific molecular abnormalities arising from genomics has opened new avenues towards the development of molecular diagnostics for RCC subtypes, and for the rational design of therapeutic approaches tailored to patients based on the molecular profiles of their tumours. Genomic studies have also pinpointed a possible role of environmental exposure to aristolochic acid, a nephrotoxin, in the genesis of the disease in some regions of central Europe. In this Review, we discuss the impact of genomics in identifying the genes and environmental exposures involved in disease susceptibility, and in discovering the molecular pathways that are disrupted somatically in different RCC subtypes. Further, we explore the possibilities provided by this genomic knowledge in providing a precision medicine approach for diagnosing and treating RCC.