FOXL2C134W : much ado about something!

J Pathol. 2022 Jan;256(1):1-3. doi: 10.1002/path.5816. Epub 2021 Nov 18.

Abstract

Recent studies have suggested that the unique FOXL2C134W mutation, which is pathognomonic for adult granulosa cell tumours of the ovary, is a tumour suppressor gene. In a recent issue of The Journal of Pathology, a detailed study by Pilsworth et al seeks to rebut the proposition that the FOXL2C134W mutation, which uniquely characterises adult granulosa cell tumours of the ovary, leads to reduced transcript levels with the implication that FOXL2 is a tumour suppressor gene. The study provides compelling evidence that both wild-type and mutant FOXL2 transcripts and protein are expressed at equivalent levels. In the context of other recent studies, one is drawn to the conclusion that FOXL2C134W is a gain-of-function mutation whose impact is mediated through enhanced interactions with the SMAD transcription factor complex. © 2021 The Pathological Society of Great Britain and Ireland.

Keywords: FOXL2; granulosa cells; ovarian cancer; ovary; stromal tumours.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Comment

MeSH terms

  • Cell Line, Tumor
  • Female
  • Forkhead Box Protein L2 / genetics
  • Forkhead Transcription Factors / genetics
  • Granulosa Cell Tumor*
  • Humans
  • Mutation
  • Ovarian Neoplasms* / genetics

Substances

  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors