Modeling YAP fusions: a paradigm for investigating rare cancers?

Genes Dev. 2022 Aug 1;36(15-16):874-875. doi: 10.1101/gad.350069.122.

Abstract

Loss of the NF2 tumor suppressor gene is a common finding in meningiomas, and more recently YAP1 fusions have been found in a subset of pediatric NF2 wild-type meningiomas. In the previous issue of Genes & Development, Szulzewsky and colleagues (pp. 857-870) showed that TEAD-dependent YAP1 activity by either the loss of the NF2 gene or YAP1-MAML2 fusion is an oncogenic process promoting meningioma tumorigenesis. Furthermore, pharmacological inhibition of YAP1-TEAD resulted in antitumor activity in both YAP1 fusion-positive and NF2 mutant meningiomas. Together, these data indicate that disruption of the YAP1-TEAD interaction raises a potential therapeutic option for these tumors that requires future investigation.

Keywords: Hippo; NF2; YAP1; YAP1-MAML2; gene fusion; meningioma.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Carcinogenesis / genetics
  • Cell Cycle Proteins / metabolism*
  • Child
  • Humans
  • Meningeal Neoplasms* / genetics
  • Meningioma* / genetics
  • Meningioma* / pathology
  • Oncogenes
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cell Cycle Proteins
  • Transcription Factors
  • YY1AP1 protein, human