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.