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Le et al. J Transl Genet Genom 2018;2:17 Journal of Translational
DOI: 10.20517/jtgg.2018.28 Genetics and Genomics

Review Open Access

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

Valerie H. Le, James J. Hsieh

Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University, St. Louis, MO 63110, USA.
Correspondence to: Dr. James J. Hsieh, Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University,
660 S. Euclid Avenue, St. Louis, MO 63110, USA. E-mail: jhsieh@wustl.edu

How to cite this article: Le VH, Hsieh JJ. Genomics and genetics of clear cell renal cell carcinoma: a mini-review. J Transl Genet Genom
2018;2:17. https://doi.org/10.20517/jtgg.2018.28
Received: 14 Sep 2018 First Decision: 17 Oct 2018 Revised: 21 Oct 2018 Accepted: 22 Oct 2018 Published: 6 Nov 2018

Science Editor: David N. Cooper Copy Editor: Cai-Hong Wang Production Editor: Zhong-Yu Guo

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

INTRODUCTION
Renal cell carcinoma (RCC) represents a heterogeneous group of malignancies derived from the kidney, of which
[1]
clear cell RCC (ccRCC) accounts for nearly 75% of cases . ccRCC is characterized by lipid- and glycogen-rich cy-
toplasm, which appears clear following histologic processing. ccRCC has generally been defined by biallelic loss of
the VHL tumor suppressor gene, located on 3p25 - loss of heterozygosity of 3p has been demonstrated in > 90% of
ccRCC cases and complete loss of the VHL gene via genetic and/or epigenetic mechanisms have been shown in
[2]
> 80% of cases . Loss of VHL leads to uncontrolled activity of hypoxia-inducible transcription factors (HIFs),
which promotes the inhibition of mitochondrion and redirection of glucose and glutamine for glycogen and
lipid synthesis, leading to the classic morphological appearance of ccRCC .
[3]
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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