Oncogenomics of Malignant Peripheral Nerve Sheath Tumors

Malignant peripheral nerve sheath tumors (MPNSTs) are a group of highly aggressive soft tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1-associated), or after radiotherapy (RT-associated). We utilized comprehensive genomic approaches and identified recurrent loss-of-function somatic alterations in the Polycomb repressive complex 2 (PRC2) core components EED or SUZ12. Genetic loss of either of these two genes results in complete loss of H3K27me3 and aberrant transcriptional programming in the affected tumors.]]> Pathologic diagnosis of maglinant peripheral nerve sheath tumors was confirmed by at least two pathologists using diagnostic formalin-fixed and paraffin-embedded sections to select cases with estimated tumor content > 70%. All patients were collected under IRB-approved protocols at Memorial Sloan Kettering Cancer Center (New York, NY, USA).]]>