RNF43 is frequently mutated in colorectal and endometrial cancers

Marios Giannakis; Eran Hodis; Xinmeng Jasmine Mu; Mai Yamauchi; Joseph Rosenbluh; Kristian Cibulskis; Gordon Saksena; Michael S Lawrence; Zhi Rong Qian; Reiko Nishihara; Eliezer M Van Allen; William C Hahn; Stacey B Gabriel; Eric S Lander; Gad Getz; Shuji Ogino; Charles S Fuchs; Levi A Garraway

doi:10.1038/ng.3127

RNF43 is frequently mutated in colorectal and endometrial cancers

Nat Genet. 2014 Dec;46(12):1264-6. doi: 10.1038/ng.3127. Epub 2014 Oct 26.

Authors

Marios Giannakis¹, Eran Hodis², Xinmeng Jasmine Mu³, Mai Yamauchi⁴, Joseph Rosenbluh³, Kristian Cibulskis⁵, Gordon Saksena⁵, Michael S Lawrence⁵, Zhi Rong Qian⁴, Reiko Nishihara⁶, Eliezer M Van Allen¹, William C Hahn¹, Stacey B Gabriel⁵, Eric S Lander⁷, Gad Getz⁸, Shuji Ogino⁹, Charles S Fuchs¹⁰, Levi A Garraway¹

Affiliations

¹ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [3] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
² 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4] Biophysics Program, Harvard University, Cambridge, Massachusetts, USA.
³ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁶ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. [4] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
⁷ 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
⁸ 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
⁹ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [3] Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 25344691
PMCID: PMC4283570
DOI: 10.1038/ng.3127

Abstract

We report somatic mutations of RNF43 in over 18% of colorectal adenocarcinomas and endometrial carcinomas. RNF43 encodes an E3 ubiquitin ligase that negatively regulates Wnt signaling. Truncating mutations of RNF43 are more prevalent in microsatellite-unstable tumors and show mutual exclusivity with inactivating APC mutations in colorectal adenocarcinomas. These results indicate that RNF43 is one of the most commonly mutated genes in colorectal and endometrial cancers.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Adenomatous Polyposis Coli Protein / genetics
Colorectal Neoplasms / genetics*
DNA-Binding Proteins / genetics*
Endometrial Neoplasms / genetics*
Exome
Female
Gene Expression Regulation, Neoplastic
Humans
Microsatellite Repeats / genetics
Mutation*
Oncogene Proteins / genetics*
Phenotype
Sequence Analysis, DNA
Signal Transduction
Ubiquitin-Protein Ligases

Substances

APC protein, human
Adenomatous Polyposis Coli Protein
DNA-Binding Proteins
Oncogene Proteins
RNF43 protein, human
Ubiquitin-Protein Ligases

Abstract

Publication types

MeSH terms

Substances

Grants and funding