9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)213-226.e3
JournalCell Reports
Volume23
Issue number1
DOIs
StatePublished - Apr 3 2018

Fingerprint

Ubiquitin
Genes
Neoplasms
Tumors
Amplification
Proteins
Atlases
Repair
Ubiquitination
Cells
DNA Repair
Molecules
Cell Cycle
DNA
Cohort Studies
Up-Regulation
Genome
Mutation
Survival

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types. / The Cancer Genome Atlas Research Network.

In: Cell Reports, Vol. 23, No. 1, 03.04.2018, p. 213-226.e3.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network. / Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types. In: Cell Reports. 2018 ; Vol. 23, No. 1. pp. 213-226.e3.
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abstract = "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.",
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author = "{The Cancer Genome Atlas Research Network} and Zhongqi Ge and Leighton, {Jake S.} and Yumeng Wang and Xinxin Peng and Zhongyuan Chen and Hu Chen and Yutong Sun and Fan Yao and Jun Li and Huiwen Zhang and Jianfang Liu and Shriver, {Craig D.} and Hai Hu and Caesar-Johnson, {Samantha J.} and Demchok, {John A.} and Ina Felau and Melpomeni Kasapi and Ferguson, {Martin L.} and Hutter, {Carolyn M.} and Sofia, {Heidi J.} and Roy Tarnuzzer and Zhining Wang and Liming Yang and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Sudha Chudamani and Jia Liu and Laxmi Lolla and Rashi Naresh and Todd Pihl and Qiang Sun and Yunhu Wan and Ye Wu and Juok Cho and Timothy DeFreitas and Scott Frazer and Borad, {Mitesh J} and Vishal Chandan and John Cheville and Copland, {John A III} and Flotte, {Thomas J} and Michael Kendrick and Jean-Pierre Kocher and O'Neill, {Brian Patrick} and Patel, {Tushar C} and Petersen, {Gloria M} and Roberts, {Lewis Rowland} and Smallridge, {Robert Christian} and Melissa Stanton and Lizhi Zhang",
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AU - The Cancer Genome Atlas Research Network

AU - Ge, Zhongqi

AU - Leighton, Jake S.

AU - Wang, Yumeng

AU - Peng, Xinxin

AU - Chen, Zhongyuan

AU - Chen, Hu

AU - Sun, Yutong

AU - Yao, Fan

AU - Li, Jun

AU - Zhang, Huiwen

AU - Liu, Jianfang

AU - Shriver, Craig D.

AU - Hu, Hai

AU - Caesar-Johnson, Samantha J.

AU - Demchok, John A.

AU - Felau, Ina

AU - Kasapi, Melpomeni

AU - Ferguson, Martin L.

AU - Hutter, Carolyn M.

AU - Sofia, Heidi J.

AU - Tarnuzzer, Roy

AU - Wang, Zhining

AU - Yang, Liming

AU - Zenklusen, Jean C.

AU - Zhang, Jiashan (Julia)

AU - Chudamani, Sudha

AU - Liu, Jia

AU - Lolla, Laxmi

AU - Naresh, Rashi

AU - Pihl, Todd

AU - Sun, Qiang

AU - Wan, Yunhu

AU - Wu, Ye

AU - Cho, Juok

AU - DeFreitas, Timothy

AU - Frazer, Scott

AU - Borad, Mitesh J

AU - Chandan, Vishal

AU - Cheville, John

AU - Copland, John A III

AU - Flotte, Thomas J

AU - Kendrick, Michael

AU - Kocher, Jean-Pierre

AU - O'Neill, Brian Patrick

AU - Patel, Tushar C

AU - Petersen, Gloria M

AU - Roberts, Lewis Rowland

AU - Smallridge, Robert Christian

AU - Stanton, Melissa

AU - Zhang, Lizhi

PY - 2018/4/3

Y1 - 2018/4/3

N2 - 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.

AB - 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.

KW - biomarker

KW - cancer prognosis

KW - FBXW7

KW - pan-cancer analysis

KW - The Cancer Genome Atlas

KW - therapeutic targets

KW - tumor subtype

KW - ubiquitin pathway

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