BRAFmutations and concurrent alterations in patients with soft tissue sarcoma

Abstract

AbstractBRAFalterations, including V600E and non‐V600E mutations and fusions, in soft tissue sarcoma (STS) have been identified in a limited case series. Here, we aimed to evaluate the frequency ofBRAFmutations and concurrent alterations in STS to understand their therapeutic action. In this retrospective analysis, we included data from 1964 patients with advanced STS who underwent comprehensive genomic profiling tests at hospitals in Japan between June 2019 and March 2023. The prevalence ofBRAFand recurrent concurrent gene alterations were also investigated.BRAFmutations were detected in 24 (1.2%) of 1964 STS patients, with a median age of 47 (range 1–69) years.BRAFV600E was detected in 11 (0.6%) of the 1964 patients with STS,BRAFnon‐V600E mutations in 9 (4.6%), andBRAFfusions were detected in 4 (0.2%).BRAFV600E was identified in 4 (0.2%) cases of malignant peripheral nerve sheath tumors. The most common concurrent alteration wasCDKN2A(11 cases, 45.8%), and the frequency was equivalent to that of theBRAFV600E (5/11 cases, 45.5%) and non‐V600E (5/9 cases, 55.6%) groups. Recurrent concurrent alterations, such asTERTpromoter mutations (7 cases, 29.2%), were detected at the same frequency in the V600E and non‐V600E groups. In contrast,TP53alterations (4/9 cases, 44.4%) and mitogen‐activated protein kinase (MAPK)‐activating genes, includingNF1,GNAQ, andGNA11(3/9 cases, 33.3%), were identified as relatively higher in the non‐V600E group than in the V600E group (each 1/11 case, 9.1%). We identifiedBRAFalterations at a rate of 1.2% in all patients with advanced STS. Among them,BRAFV600E andBRAFfusions account for 45.8% and 16.7%, respectively. Collectively, our findings support the clinical characteristics and therapeutic strategies for patients withBRAF‐altered advanced STS.