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RNF43 is frequently mutated in colorectal and endometrial cancers


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.

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Figure 1: RNF43 mutations in colorectal and endometrial cancers.
Figure 2: Association of RNF43 mutations with MSI status and APC mutations.

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We thank S. Bahl, E. Nickerson and S. Chauvin for project management and A. Regev for help with computing resources, as well as A. Sivachenko, F. Huang and P. Tamayo for helpful discussions. This work was supported by the Dana-Farber Cancer Institute Leadership Council, the 2014 Colon Cancer Alliance–American Association for Cancer Research Fellowship for Biomarker Research, grant 14-40-40-GIAN, the Perry S. Levy Endowed Fellowship (M.G.), award T32GM007753 from the National Institute of General Medical Sciences, the Herchel Smith Fellowship (E.H.) and the Agrusa Fund for Colorectal Cancer Research (C.S.F.), as well as National Human Genome Research Institute grant U54HG003067 (E.S.L. and S.B.G.) and National Cancer Institute grants, K07CA190673 (R.N.), P01CA87969, UM1CA167552 and R01CA151993 (S.O.), R01CA118553 and R01CA168141 (C.S.F.) and P50CA127003 (M.G., W.C.H., L.A.G. and C.S.F.).

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M.G., E.H., W.C.H., G.G., S.B.G., E.S.L., S.O., C.S.F. and L.A.G. designed research. M.G., E.H., X.J.M., M.Y., J.R., K.C., G.S., M.S.L., Z.R.Q., R.N. and E.M.V.A. performed research. G.G., S.B.G., E.S.L., S.O. and C.S.F. contributed new reagents and analytic tools. M.G., E.H., X.J.M., E.M.V.A. and L.A.G. analyzed data. M.G., E.H. and L.A.G. wrote the manuscript.

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Correspondence to Levi A Garraway.

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Competing interests

L.A.G. is a consultant for an equity holder in Foundation Medicine. L.A.G. is also a consultant to Novartis, Millenium/Takeda and Boehringer Ingelheim and is a recipient of a grant from Novartis.

Integrated supplementary information

Supplementary Figure 1 Manual review of RNF43 p.Gly659fs mutations using Integrated Genomics Viewer and validation by Sanger sequencing.

Representative Integrated Genomics Viewer screenshots and Sanger sequencing chromatograms for RNF43 p.Gly659fs-mutated tumor (a,c) and matched normal (b,d) tissue.

Supplementary information

Supplementary Text and Figures

Manual review of RNF43 G659fs mutations using Integrated Genomics Viewer and validation by Sanger sequencing. (PDF 262 kb)

Supplementary Tables 1–10

Supplementary Tables 1–10 (XLSX 35911 kb)

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Giannakis, M., Hodis, E., Jasmine Mu, X. et al. RNF43 is frequently mutated in colorectal and endometrial cancers. Nat Genet 46, 1264–1266 (2014).

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