Distribution of somatic mutations and mutation types in BRAF gene across The Cancer Genome Atlas Pan-Cancer analysis project.
Top panel shows the relative frequency of non-silent somatic mutations (number of observed type of somatic mutation/cohort size) of detected mutations across different human cancer tissues within TCGA. Bottom panel shows fraction of mutations sorted by affected protein domains of BRAF. The analysis includes all non-silent (protein coding missense, indels, frame-shift, stop, splice site) mutations and distinguishes mutations of V600E in purple, ATP binding site in yellow, all mutations in the protein kinase (PK) domain of BRAF but not V600E or ATP binding site in pink, RAS-binding domain (RBD) in blue and remaining protein sequence (other) in grey. The PAN-cancer analysis covers cancer tissues: adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), colon adenocarcinoma (COAD), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), acute myeloid leukemia (LAML), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), skin cutaneous melanoma (SKCM), stomach adenocarcinoma (STAD), thyroid adenocarcinoma (THCA), uterine corpus endometrioid carcinoma (UCEC) and uterine carcinosarcoma (UCS). Right box within panels includes analysis for PAN-cancer cohort and sub-cohort that excludes BRAF-rich cancers of more than 0.5 relative frequency, like SKCM and THCA, or of more than 50% V600E BRAF, like THCA, COAD, SKCM, GBM (TCGA*). Patient stratification: Bars below the panels mark stratification strategy of human cancers based on their BRAF genotype. A BRAF-V600E mutation; B BRAF mutation in protein kinase domain other than V600E; C BRAF-mutation in protein kinase domain; D BRAF-mutation other than protein kinase or RBD; E no BRAF mutation.