Fig. 3: MTBP functional classification of variants in the Cancer Core Europe cohort.
a, Functional classification of the tumor mutations observed in the CCE cohort (variants assumed to be functionally neutral, such as common polymorphisms, are not included here). Colors represent the different sources of supporting evidence used by the MTBP (Fig. 2). The upper pie chart represents overall counts of mutations, whereas the lower pie chart represents counts of unique mutations. b, Functional classification of the tumor mutations (represented as in a) observed across several of the most recurrently mutated cancer genes in the CCE cohort. Tumor suppressors tend to accumulate a variety of null events (e.g., frameshift or nonsense variants) whose effect is mainly estimated by bona fide biological assumptions, except for genes that have been more exhaustively characterized by ongoing efforts (e.g., BRCA1 and BRCA2) and/or are enriched by specific dominant-negative mutations (e.g., TP53 and, to a lesser extent, PTEN). In oncogenes, variants are concentrated in few hotspots with a well-known gain-of-function consequence in some genes (e.g., KRAS and BRAF), whereas others show a diversity of mutations whose effect remains unclassified in a considerable number of cases (e.g., ERBB2 and FGFR3). MoA, mechanism of action.
