A genetic mouse model with postnatal Nf1 and p53 loss recapitulates the histology and transcriptome of human malignant peripheral nerve sheath tumor.

ABSTRACT:

Background

Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas. Somatic inactivation of NF1 and cooperating tumor suppressors, including CDKN2A/B, PRC2, and p53, is found in most MPNST. Inactivation of LATS1/2 of the Hippo pathway was recently shown to cause tumors resembling MPNST histologically, although Hippo pathway mutations are rarely found in MPNST. Because existing genetically engineered mouse (GEM) models of MPNST do not recapitulate some of the key genetic features of human MPNST, we aimed to establish a GEM-MPNST model that recapitulated the human disease genetically, histologically, and molecularly.

Methods

We combined 2 genetically modified alleles, an Nf1;Trp53 cis-conditional allele and an inducible Plp-CreER

SUBMITTER: Inoue A 

PROVIDER: S-EPMC8500687 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature