Extended Data Fig. 9: Comparison of oncogenic MMs between primary and metastatic samples across cancers.

a, Distribution of cancer types for metastatic samples included in the total, TCGA and TARGET, FM and GENIE cohorts. Cancer types with less than 1% frequency were combined as ‘OTHERS’ in each cohort. Cancer-type abbreviations are listed in Supplementary Table 1. b, Comparison of the frequency of MM⁺ samples in primary and metastatic samples across 14 MM⁺ oncogenes in the total cohort. c, Distribution of EGFR and KIT hotspot/functional mutations in primary and metastatic samples in NSCLC and GIST, respectively. Acquired TKI-resistant mutations are indicated in red. d, Frequency of MM⁺ samples for EGFR and KIT in primary and metastatic samples. e, f, Fraction of MM⁺ mutations for missense mutations and in-frame indels (e) and major and minor hotspots (f) in EGFR and KIT in recurrently mutated cancer types in metastatic samples. b, d–f, Two-sided Fisher’s exact test. g, Number of MMs according to mutational combinations in EGFR in recurrently mutated cancer types in metastatic samples (n = 81). Red and black circles indicate, respectively, observed and expected (median with 95% confidence intervals) values. Two-sided simulation test (n = 10,000) with Benjamini–Hochberg correction. d–g, After exclusion of acquired TKI-resistant mutations, including EGFR T790M in NSCLC and KIT V654, T670, C809, D816, D820, N822 and Y823 missense mutations in GIST. Examined numbers are shown in parentheses.