Genomics and genetics of clear cell renal cell carcinoma: a mini-review

Abstract

Renal cell carcinoma (RCC) represents a heterogeneous group of malignancies derived from the kidney, of which clear cell RCC (ccRCC) accounts for nearly 75% of cases. Despite major advances in effective therapies, metastatic ccRCC is still associated with a 10%-20% 5-year survival and remains quite lethal. Great effort has been placed into understanding the genetics and genomics of ccRCC and their prognostic and therapeutic implications. Large-scale cancer genomics sequencing studies have identified several driver genes beyond VHL, particularly PBRM1 (40%), SETD2 (15%), and BAP1 (10%), drastically changing the concept of single-gene pathology underlying sporadic ccRCC. In this mini-review, we explore the pathways by which the loss of VHL, PBRM1, SETD2, and/or BAP1 induce ccRCC through discussion of gene function, disease models, prognostic indications, and therapeutic advances.

Keywords

Kidney cancer / oncogene / tumor suppressor gene / VHL / HIF / PBRM1 / BAP1 / MTOR

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