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RNF43 truncating mutations have similar transcriptional profiles to BRAF missense mutations.

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posted on 2021-07-02, 17:36 authored by Alexis M. Thornton, Lishan Fang, April Lo, Maria McSharry, David Haan, Casey O’Brien, Alice H. Berger, Marios Giannakis, Angela N. Brooks

(A) LURE oncoprint of known driver BRAF missense mutations, which activate the MAPK/RTK pathways, used as “bait” in TCGA COAD. LURE finds RNF43 truncating events as a “catch” event [35]. (B) Kruskal Wallis test of LURE classifier scores across samples with different BRAF and RNF43 status. ns: 5.00e-02 < p < = 1.00e+00, *: 1.00e-02 < p < = 5.00e-02, **: 1.00e-03 < p < = 1.00e-02, ***: 1.00e-04 < p < = 1.00e-03, ****: p < = 1.00e-04) (C) Lollipop plots [20] showing the frequency RNF43-truncating mutations identified as catches (classifier score > 0.5) with LURE in the TCGA COAD cohort. The ZNRF-3 ectodomain is indicated in green and the ring finger domain is indicated in red (D) LURE classifier scores across the samples that have a single RNF43 truncating event and no co-occuring BRAF events (E) Model summarizing the predicted impacts of the RNF43 R117fs and RNF43 G659fs variants.