202 Molecular Signature of Malignant Peripheral Nerve Sheath on Tumor Site

INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNSTs) are rare, highly aggressive soft tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1) or after radiotherapy (RT). High recurrence rates and distant metastases are common, with lung and bone being the most common sites, yet the anatomic distribution of molecular changes is largely unknown. METHODS: Using the cBioPortal platform and systematic bioinformatical-analysis of the Cancer Genome Atlas (MSKCC) Nature Genetics 2014 dataset, we screened the dataset for the ADAM3A gene in the completed gene panel and twelve MPNST patients [pulmonary (6), neck (1), chest-wall (2), calf (1), arm (2)] with were included in the study. Broadly, these twelve patients were categorized as primary-pulmonary MPNST (6) and non-pulmonary MPNST (6) subgroups. RESULTS: The putative copy-number alteration pattern involving the ADAM3A gene based on the primary site was distinct (p <0.0001). All six patients with primary-pulmonary MPNST showed ADAM3A amplification while all six patients with non-pulmonary MPNST demonstrated ADAM3A homodeletion. Remarkably, regardless of the underlying etiology and pathogenesis, ADAM3A amplification in primary-pulmonary MPNST was invariably noted across the board in sporadic (3), NF1-associated (2), and RT-associated (1) tumor samples (p <0.0001). CONCLUSIONS: The findings in this study highlight the site-specificity of the MPNST molecular landscape. Further studies are essential for understanding the underlying molecular implications, pathways, and the specific role of ADAM3A in pulmonary and non-pulmonary MPNSTs.