Prevalence and detection of actionable BRAF V600 and NRAS Q61 mutations in malignant peripheral nerve sheath tumor by droplet digital PCR

Malignant peripheral nerve sheath tumors ( MPNSTs) are aggressive tumors with poor prog-nosis that do not typically respond well to standard chemotherapy. Recently, point mutations involving BRAF V600E have been demonstrated in a subset of MPNST, offering the possibility of targeted treat-ment. However, the reported prevalence of these alterations is variable. Mutations involving NRAS, which is also involved in the MAPK/ERK pathway and amenable to targeted inhibitors, have not been well characterized in MPNST. In this study, we validated droplet digital polymerase chain reaction for the detection of BRAF V600E and NRAS Q61 mutations and evaluate the prevalence of BRAF V600E and NRAS Q61 mutations in 79 cases of MPNST, including 45 sporadic, 27 NF-1 associated, and 7 radiation-associated tumors. We detected actionable BRAF or NRAS mutations in 3 of 44 sporadic MPNSTs (6.8%), including 2 BRAF V600 and 1 NRAS Q61 mutations, as well as 1 NRAS Q61 muta-tion in a tumor that was ultimately considered to represent melanoma. These 3 cases with positive mu-tations were exclusively in sporadic, high-grade MPNST (FNCLCC grade 3 of 3), with a prevalence of 11.5% in this group (3.8% NRAS Q61 mutations and 7.7% BRAF V600 mutations). None of the tumors associated with NF-1 or prior radiation had detectable mutations in the genes tested. Overall, the prev-alence of these alterations offers the possibility of targeted therapy in this aggressive type of sarcoma and suggests the potential benefit of routine clinical testing.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors that do not respond well to standard chemotherapy. However, recent studies have found that a subset of MPNSTs may have point mutations in the BRAF V600E and NRAS Q61 genes, which could be targeted for treatment. This study validated a PCR method for detecting these mutations and found a prevalence of approximately 6.8% in 79 cases of MPNST.