2016 Children's Tumor Foundation conference on neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis

Abstract

Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. The transformation from plexiform neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) is being clarified, along with new management and treatments for benign and premalignant tumors. Promising new cellular and in vivo models for understanding the musculoskeletal abnormalities in NF1, the development of NF2 or SWN associated schwannomas, and clarifying the cells that give rise to NF1-associated optic pathway glioma were presented. The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. Novel promising imaging techniques are being developed, as well as new integrative and holistic management models for patients that take into account psychological, social, and biological factors. Importantly, new therapeutic approaches for schwannomas, meningiomas, ependymomas, PNF, and MPNST are being pursued. This report highlights the major advances that were presented at the 2016 CTF NF conference.

CAR-T Cells: The Next Generation Cancer Therapy

“…These include the presence of bilateral vestibular schwannomas (VS), as was the case in this patient [1][2][3][4]. Her initial manifestation was with bilateral proptosis, possibly due to intraorbital involvement of the III cranial nerves with schwannomata as they are prone to do [2], or else due to meningiomas.…”

“…We are not aware of any reports in the literature of the occurrence of hemangioblastomas in the setting of a case of NF2. The genetic basis for these conditions has been well described [1][2][3][4]. This patient presents with a hemangioblastoma in addition to the classic picture of NF2 with bilateral vestibular schwannomas and multiple other tumours around the brain.…”

“…Her initial manifestation was with bilateral proptosis, possibly due to intraorbital involvement of the III cranial nerves with schwannomata as they are prone to do [2], or else due to meningiomas. NF2 is associated with multiple tumours, primarily intracranial schwannomas and meningiomas, as well as spinal ependymomas [2,4]. For this reason, it is also referred to as the MISME (multiple inherited Schwanommas, meningiomas and ependymomas) syndrome (Figure 3).…”

Visceral plexiform schwannoma: A case series

“…Genetic studies are useful when there is a positive family history or in case of a certain association with NF-schwannomatosis. In these selected patients, attempts have been made to use DNA next-generation sequencing to detect copy number alterations and mosaicisms and to correlate genotype with clinical phenotype (14). This may lead to a better understanding of the underlying pathology and to the development of new clinical models (e.g., germline mutations of SMARCB1 predispose to schwannomas) (15).…”

Age-related schwannomatosis with potential exosome-mediated contribution to prostate hyperplasia: a case report and mini-review

“…Both schwannomatosis and neurofibromatosis type 2 (NF2) diseases are characterized by the onset of multiple schwannomas, and have often diagnostic overlaps even after basic molecular diagnosis, thereby necessitating complementary refined genomic and epigenomic characterization in order to clarify the cases. 22,32,33 As recently reviewed, 23,34 both schwannomatosis and NF2 are autosomal dominant syndromes caused by the constitutional mutation of one tumor suppressor gene ( NF2, SMARCB1 or LZTR1 ) that predispose the development of multiple schwannomas through somatic inactivation of the relevant remaining wild type allele either alone (NF2) or in combination with the somatic biallelic inactivation of NF2 ( SMARCB1 - or LZTR1 -associated schwannomatosis). The NF2 gene is thus involved in both cases either alone as the constitutional mutant (NF2) or as the somatic biallelic mutant associated with either the SMARCB1 or LZTR1 mutant gene (schwannomatosis).…”