Class III BRAF mutations highly occurred with RAS mutations.
We analyzed publicly available somatic mutation data from 65853 patients across different cancer types (http://cbioportal.org) (Table 2, Supplemental Figure S3). We found only 1606 patients with class I BRAF mutations, around 95% of them bearing BRAF V600E mutations and 4% co-expressed RAS mutations with frequencies 0.37%, 2.5% and 0.8% for HRAS, NRAS and KRAS respectively. In addition, we identified 289 patients with class II BRAF mutations. Of them; ~17% co-expressed RAS mutations with frequencies 2.77%, 3.8% and 10.38% for HRAS, NRAS and KRAS respectively. Conversely, 286 patients with class III BRAF mutations were found, 24% of them co-expressed RAS mutations with frequencies 3.85%, 8.74% and 11.5% for HRAS, NRAS and KRAS respectively. The class III mutation N581I that was detected in our patients co-occurred with RAS mutations in around third of the cases (33%). Of these cases 6.67%, 6.67% and 20% co-occurred with HRAS, NRAS and KRAS respectively.
We investigated the frequency of the three BRAF mutation classes in sarcomas, the overall number of sarcoma patients with BRAF mutations is 25 patients, of them; five patients with class I BRAF mutation (0, 0 and 1 co-occurred with HRAS, NRAS and KRAS respectively), four with class II BRAF mutations (0, 1 and 0 co-occurred with HRAS, NRAS and KRAS respectively), and two patients with class III mutations (0, 0 and 0 co-occurred with HRAS, NRAS and KRAS respectively). While the remaining are with other mutation types including intergenic and fusion BRAF genes.
Looking at the overall occurrence of the BRAF mutations in RMS, we identified two RMS patients with class I, class II mutations across all the datasets and none of them co-occurred with HRAS mutations. Highlighting the very rare occurrence of BRAF mutations in RMS.