Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Authors

Zhongqi Ge, University of Texas MD Anderson Cancer Center
Jake S. Leighton, University of Texas MD Anderson Cancer Center
Yumeng Wang, University of Texas MD Anderson Cancer Center
Xinxin Peng, University of Texas MD Anderson Cancer Center
Zhongyuan Chen, University of Texas MD Anderson Cancer Center
Hu Chen, University of Texas MD Anderson Cancer Center
Yutong Sun, University of Texas MD Anderson Cancer Center
Fan Yao, University of Texas MD Anderson Cancer Center
Jun Li, University of Texas MD Anderson Cancer Center
Huiwen Zhang, University of Texas Health Science Center at Houston
Jianfang Liu, Chan Soon-Shiong Institute of Molecular Medicine at Windber
Craig D. Shriver, Walter Reed National Military Medical Center
Hai Hu, Chan Soon-Shiong Institute of Molecular Medicine at Windber
Samantha J. Caesar-Johnson
John A. Demchok
Ina Felau
Melpomeni Kasapi
Martin L. Ferguson
Carolyn M. Hutter
Heidi J. Sofia
Roy Tarnuzzer
Zhining Wang
Liming Yang
Jean C. Zenklusen
Jiashan (Julia) Zhang
Sudha Chudamani
Jia Liu
Laxmi Lolla
Rashi Naresh
Todd Pihl
Qiang Sun
Yunhu Wan
Ye Wu

Document Type

Journal Article

Publication Date

4-3-2018

Journal

Cell Reports

Volume

23

Issue

1

DOI

10.1016/j.celrep.2018.03.047

Keywords

biomarker; cancer prognosis; FBXW7; pan-cancer analysis; The Cancer Genome Atlas; therapeutic targets; tumor subtype; ubiquitin pathway

Abstract

© 2018 The Authors Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development.

APA Citation

Ge, Z., Leighton, J., Wang, Y., Peng, X., Chen, Z., Chen, H., Sun, Y., Yao, F., Li, J., Zhang, H., Liu, J., Shriver, C., Hu, H., Caesar-Johnson, S., Demchok, J., Felau, I., Kasapi, M., Ferguson, M., Hutter, C., Sofia, H., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J., Zhang, J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., & Wu, Y. (2018). Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types. Cell Reports, 23 (1). http://dx.doi.org/10.1016/j.celrep.2018.03.047