Genomic Profiling in Patients With Malignant Peripheral Nerve Sheath Tumors Reveals Multiple Pathways With Targetable Mutations

Proto-Oncogene Proteins B-raf 0301 basic medicine Neurofibromin 1 Neurofibromatoses DNA Mutational Analysis Antineoplastic Agents Genomics Middle Aged Nerve Sheath Neoplasms 3. Good health Gene Expression Regulation, Neoplastic 03 medical and health sciences Genes, ras Chemotherapy, Adjuvant Mutation Biomarkers, Tumor Humans Female Radiotherapy, Adjuvant Molecular Targeted Therapy Protein Kinase Inhibitors Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p15
DOI: 10.6004/jnccn.2018.7033 Publication Date: 2018-08-11T17:15:16Z
ABSTRACT
Background: The aim of this study was to determine the frequency alterations in BRAF and other RAS/RAF genes, as well targetable pathways malignant peripheral nerve sheath tumors (MPNSTs). Patients Methods: Pathology specimens were available for 2 cohorts: (1) patients with MPNST at Swedish Cancer Institute (n=17) from 2004 through 2016, (2) evaluated >300 genomic Foundation Medicine 2014 2016 (n=186; including BRAF-mutated MPNST). Results: Of 201 MPNSTs, 13 (6.5%) demonstrated alterations. In cohort, 10 84 (11.9%) no NF1 had mutations (5 V600E, 5 other), did 3 102 (2.9%) (1 other). 47% an alteration least one gene pathway (not or BRAF); 46% PI3 pathway, 70% having 1 pathways; 57% a CDKN2A (80% 71% NF1-altered patients); DNA repair genes. MPNST, both wild-type NF1-mutated, often harbor changes related CDKN2A/B. V600E occur BRAF, suggesting need second-generation activating inhibitors. concurrence and/or CDKN2A/B mutations, particular, may be significant transformation neurologic benign malignant. Conclusions: All MPNSTs would benefit comprehensive analysis. Treatments targeted RAS/RAF, repair, should used developed treat uncommon tumor.
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