Overexpression of PDGFRA cooperates with loss of NF1 and p53 to accelerate the molecular pathogenesis of malignant peripheral nerve sheath tumors.

ABSTRACT: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, frequently metastatic sarcomas that are associated with neurofibromatosis type 1 (NF1), a prominent inherited genetic disease in humans. Although loss of the NF1 gene predisposes to MPNST induction, relatively long tumor latency in NF1 patients suggests that additional genetic or epigenetic abnormalities are needed for the development of these nerve sheath malignancies. To study the molecular pathways contributing to the formation of MPNSTs in NF1 patients, we used a zebrafish tumor model defined by nf1 loss in a p53-deficient background together with the overexpression of either wild-type or constitutively activated PDGFRA (platelet-derived growth factor receptor-α) under control of the sox10 neural crest-specific promoter.

SUBMITTER: Ki DH 

PROVIDER: S-EPMC5332555 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature