Genetic alteration of histone lysine methyltransferases and their significance in renal cell carcinoma

Libin Yan; Yangjun Zhang; Beichen Ding; Hui Zhou; Weimin Yao; Hua Xu

doi:10.7717/peerj.6396

Genetic alteration of histone lysine methyltransferases and their significance in renal cell carcinoma

PeerJ. 2019 Feb 6:7:e6396. doi: 10.7717/peerj.6396. eCollection 2019.

Authors

Libin Yan^{1

2}, Yangjun Zhang^{1

2}, Beichen Ding^{1

2}, Hui Zhou^{1

2}, Weimin Yao^{1

2}, Hua Xu^{1

2}

Affiliations

¹ Urology, Tongji Hospital,Tongji Medical College, Huazhong University of Science Technology, Wuhan, Hubei, China.
² Institute of Urology of Hubei Province, Wuhan, China.

Abstract

Background: Histone lysine methyltransferases (HMTs), a category of enzymes, play essential roles in regulating transcription, cellular differentiation, and chromatin construction. The genomic landscape and clinical significance of HMTs in renal cell carcinoma (RCC) remain uncovered.

Methods: We conducted an integrative analysis of 50 HMTs in RCC and discovered the internal relations among copy number alterations (CNAs), expressive abundance, mutations, and clinical outcome.

Results: We confirmed 12 HMTs with the highest frequency of genetic alterations, including seven HMTs with high-level amplification, two HMTs with somatic mutation, and three HMTs with putative homozygous deletion. Patterns of copy number and expression varied among different subtypes of RCC, including clear cell renal cell carcinoma, papillary cell carcinoma, and chromophobe renal carcinoma. Kaplan-Meier survival analysis and multivariate analysis identified that CNA or mRNA expression in some HMTs were significantly associated with shorter overall patient survival. Systematic analysis identified six HMTs (ASH1L, PRDM6, NSD1, EZH2, WHSC1L1, SETD2) which were dysregulated by genetic alterations as candidate therapeutic targets.

Discussion: In summary, our findings strongly evidenced that genetic alteration of HMTs may play an important role in generation and development of RCC, which lays a solid foundation for the mechanism for further research in the future.

Keywords: HMTs; RCC.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81470935, 81370805, 81670645, 81602236), the Chenguang Program of Wuhan Science and Technology Bureau (2015070404010199, 2015071704021644), and the National High Technology Research and Development Program 863 (2014AA020607). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.