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

• DOI: 10.6004/jnccn.2018.7033
• Publication Date: 2018-08-11T17:15:16Z
• Authors: Henry G. Kaplan; Steven Rostad; Jeffrey S. Ross; Siraj M. Ali; Sherri Z. Millis
• Keywords: 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

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.