Prevalence of class I-III BRAF mutations among 114,662 cancer patients in a large genomic database

Abstract

These data represent the largest aggregation of BRAF mutations within a single clinical database to our knowledge. The relative proportions of both BRAF V600 mutations and non-V600 mutations are informative in all cancers and by malignancy, and can serve as a definitive gold-standard for BRAF mutation cancer incidence by malignancy. The rate of BRAF mutation in human cancer in a real-world large database is lower than previously reported likely representing testing more broadly across tumor types. The relative percentages of Class II and Class III BRAF mutations are higher than previously reported, representing almost 35% of BRAF mutations in cancer. These findings provide support for the development of effective treatments for non-V600 BRAF mutations in cancer.

Keywords: BRAF; Cancer; biomarkers; colon; kinase; melanoma.

Figure 1.

Prevalence of class 1, 2, and 3 BRAF mutations in various cancer types.

Figure 2.

Relative proportion of classes of BRAF mutation by tumor type.

Figure 3.

Type and frequency of mutations seen in the database in the BRAF protein. Mutations are plotted along the transcript of the protein by location in the transcript. Individual points (“lollipops”) represent the number of mutations at the specific amino acid locus seen in the database. Lollipop color is by class of mutation. Of note, Class 1 mutations are limited to the V600 locus, while class 2 and 3 mutations occur at various other points along the transcript. RBD: Raf-like RAS binding domain; C1_1: phorbol esters/diacylglycerol binding domain (binds the secondary messengers that can stimulate PKC); Pkinase_Tyr: protein tyrosine kinase domain. Figure adapted from cBioportal Mutation Mapper (https://www.cbioportal.org/mutation_mapper).