We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with overexpression of HIF1α and HIF2α in the tumors (P = 0.01 and 0.04, respectively). Our findings highlight the potential contribution of UMPP to ccRCC tumorigenesis through the activation of the hypoxia regulatory network.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Rini, B.I., Campbell, S.C. & Escudier, B. Lancet 373, 1119–1132 (2009).
van Haaften, G. et al. Nat. Genet. 41, 521–523 (2009).
Dalgliesh, G.L. et al. Nature 463, 360–363 (2010).
Varela, I. et al. Nature 469, 539–542 (2011).
Gui, Y. et al. Nat. Genet. 43, 875–878 (2011).
Forbes, S.A. et al. Curr. Protoc. Hum. Genet. Chapter 10, Unit 10.11 (Wiley, 2008).
Getz, G. et al. Science 317, 1500 (2007).
Szymanska, K. et al. Cancer Lett. 293, 92–98 (2010).
Banks, R.E. et al. Cancer Res. 66, 2000–2011 (2006).
Harbour, J.W. et al. Science 330, 1410–1413 (2010).
Lamb, R.F. et al. Nat. Cell Biol. 2, 281–287 (2000).
Ding, L. et al. Nature 455, 1069–1075 (2008).
Sonoda, I. et al. Cancer Res. 64, 3741–3747 (2004).
Linehan, W.M. et al. Annu. Rev. Med. 61, 329–343 (2010).
This work was supported by the National Basic Research Program of China (973 program 2011CB809200), the National Natural Science Foundation of China (30725008, 30890032 and 30811130531), the Chinese 863 program (2006AA02A301, 2006AA02A302 and 2009AA022707), the Shenzhen Municipal Government of China (JC200903190767A, JC200903190772A, ZYC200903240076A, CXB200903110066A, ZYC200903240077A and ZYC200903240080A), the Promotion Program for Shenzhen Key Laboratory, Shenzhen, China (CXB200903090055A and CXB201005250016A) and the Biobank of Complex Diseases in Shenzhen (CXC201005260001A). This project was also funded by the Shenzhen municipal government and the local government of the Yantian District of Shenzhen.
The authors declare no competing financial interests.
About this article
Cite this article
Guo, G., Gui, Y., Gao, S. et al. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet 44, 17–19 (2012). https://doi.org/10.1038/ng.1014
Genomics, Proteomics & Bioinformatics (2021)
Improved cancer biomarkers identification using network-constrained infinite latent feature selection
PLOS ONE (2021)
Clinical Kidney Journal (2021)
Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis
BioMed Research International (2020)
A transcriptomic analysis of Nsmce1 overexpression in mouse hippocampal neuronal cell by RNA sequencing
Functional & Integrative Genomics (2020)