Extended Data Fig. 8: Cancer-type-specific oncogenic MMs.

a, Distribution of FGFR3 mutations in samples with single and multiple mutations in recurrently mutated cancer types (defined as those with 20 or more hotspot/functional mutations) in primary samples from the total cohort. Mutations specific to MM⁺ samples are indicated in red. b, Cancer-type-specific analysis of MM⁺ oncogenes identified by pan-cancer analysis. Shown are numbers of MM⁺ samples for MM⁺ oncogenes in the corresponding cancer type from the discovery cohort (with q < 0.01 and three or more MMs). Red and black circles indicate, respectively, observed and expected (median with 95% confidence intervals) values. One-sided permutation test (n = 10,000) with Benjamini–Hochberg correction. c, Proportion of mutations according to type, position and amino-acid change, in six cancer-type-specific MM⁺ oncogenes in the corresponding cancer type. Asterisk, AML, and dagger, BALL were analysed in primary samples from the total cohort and (an) independent set(s) of patients^{29,30,31,32,33}. d, e, Distribution of hotspot/functional mutations (d) and frequency of MM⁺ samples (e) in NOTCH1 for TALL and CLL in primary samples from the total cohort. An independent cohort³⁴ was also analysed for CLL. f, Significant pairwise associations (q < 0.01) with observed/expected ratios among functional domains (n = 65). Orange and blue colours depict co-occurring (observed number of MMs significantly higher than expected) and mutually exclusive (lower than expected) associations. Two-sided simulation test (n = 10,000) with Benjamini–Hochberg correction. g, Fraction of MM⁺ mutations for missense mutations and in-frame indels (consisting mainly of internal tandem duplications, ITDs) as well as distribution of mutations and fraction of MM⁺ mutations for each hotspot/functional position (the top ten are shown) in FLT3 for AML in primary samples from the total cohort and an independent set of patients. h, Distribution of mutations and fraction of MM⁺ mutations for each hotspot/functional position in JAK2 for BALL in primary samples from the total cohort and independent sets of patients. g, h, Asterisks indicate major positions (in which 10% or more of all mutations were present). e, g, h, Two-sided Fisher’s exact test. Examined numbers are shown in parentheses.