Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors for which no established systemic treatment exists. MPNSTs occur in approximately 10% of patients with neurofibromatosis type 1, with malignancy usually present in the third or fourth decade of life.1 When MPNSTs occur sporadically in the absence of neurofibromatosis, they tend to present later in life, usually in the sixth or seventh decade, and often without an inactivating alteration in neurofibromin (NF1), which is seen in patients with neurofibromatosis type 1. Wild-type NF1 protein exhibits an inhibitory effect on the RAS/RAF pathway. Such tumors exhibit increased activity in the RAS/RAF pathway by the lack of negative feedback.2 Alterations in the PI3K/PTEN/AKT pathway can also affect RAS/RAF activity3 and can be stimulated by similar stimuli as the RAS/RAF pathway.
Previously, we reported on a patient with a sporadic MPNST, whose tumor featured a BRAF V600E mutation.4 This mutation results in activation of BRAF, leading to increased activity of the RAS/RAF pathway.5 This patient had a dramatic response to vemurafenib, an inhibitor of BRAF V600E. As a result, in the current study we analyzed the presence of BRAF alterations, other RAS/RAF alterations, and other genomic alterations in all MPNSTs studied at Swedish Cancer Institute and Foundation Medicine during the past 12 years.
Drs. Ross, Ali, and Millis are employees of Foundation Medicine, Inc. Drs. Ali and Ross have equity interest in Foundation Medicine, Inc. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
This study was supported in part by the Kaplan Cancer Research Fund.
See JNCCN.org for supplemental online content.
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. Schindler G Capper D Meyer J Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma, and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 2011; 121: 397– 405.
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