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Review
. 2016 May;18(5):624-38.
doi: 10.1093/neuonc/nov200. Epub 2016 Feb 6.

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis

Jaishri O Blakeley  1 , Scott R Plotkin  1
Affiliations
Review

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis

Jaishri O Blakeley et al. Neuro Oncol. 2016 May.

Abstract

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations.

Keywords: NF1; NF2; schwannomatosis; therapeutics; tumor suppressor syndrome.

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Figures

Fig. 1.
Fig. 1.
Common manifestations of neurofibromatosis type 1 including: (A) multiple café-au-lait macules, (B) skin fold freckling with a café-au-lait macule, (C) cutaneous neurofibromas and plexiform neurofibromas that are nodular (D1), diffuse (D2) and multifocal and infiltrating (D3).
Fig. 2.
Fig. 2.
Cranial MRI scans of patients with neurofibromatosis type 2 demonstrating bilateral vestibular schwannomas and multiple meningiomas.
Fig. 3.
Fig. 3.
Representative MRI scan of the multiple schwannomas in a patient with schwannomatosis. Schwannomas appear hyperintense on T2-weighted images and enhance after administration of gadolinium contrast. The enhancement pattern can range from homogenous to heterogenous. Cysts may develop within some tumors.
See this image and copyright information in PMC

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Publication types

Supplementary concepts