Fig. 1

The genomic features of tumors with Class1 BRAF mutations are more unique than those with Class2/3 mutations. A The positions of detected mutations in each class (Class1: green; Class2: purple; Class3: orange) along the tyrosine kinase domain of BRAF gene are illustrated by the lollipop chart, whose frequencies are shown by the pie charts. B The proportion of patients with genomic alterations across three BRAF classes. All genes whose mutational frequencies were over 10% in either Class1 or 2 or 3 subgroup were included for analysis and significant genes (p < 0.05 based on Fisher’s exact test) are grouped based on enrichment patterns indicated below the gene names (e.g., Class1 vs. Class2/3 subgroup includes genes whose mutational frequencies were significantly different in Class1 compared to both Class2 and Class3). Genes involved in PI3K, RTK/RAS, and Wnt signaling pathway are colored in orange, blue, and red, respectively, and the rest significant genes are black. C Frequencies of pathway alterations by BRAF classes. D Frequencies of patients harboring KRAS/NRAS/HRAS activation mutations are shown in each BRAF class. The allele frequency differences between RAS-active mutation and BRAF mutation are labeled by slash (BRAF > RAS) and dots (BRAF < RAS), respectively. E Mutational signature analysis was performed based on the COSMIC database. APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like enzyme) is associated with Signature 2 and Signature 13, and NER (nucleotide excision repair) is related to Signature 22. Statistical analyses are performed between all pairs of subgroups using the Mann-Whitney test and the significant p (< 0.05) values are labeled. F The levels of TMB in BRAF-wt and three BRAF classes are shown by the boxplot and the significant p (< 0.05) values based on the Mann-Whitney test are labeled. G Percentage of MSI-H patients by BRAF status and Fisher’s exact tests are performed in all pairs of comparison. Abbreviation: RBD: receptor-binding domain; DIF: dimerization interface; CL: catalytic loop; DFG: Asp-Phe-Gly motif; AS: activation segment