APC germline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings?

J Med Genet. 2023 May;60(5):460-463. doi: 10.1136/jmg-2022-108467. Epub 2022 Oct 21.

Abstract

APC germline pathogenic variants result in predisposition to familial adenomatous polyposis and extraintestinal tumours such as desmoid fibromatosis, medulloblastomas and thyroid cancers. They have also been recently involved in ovarian microcystic stromal tumours. APC inactivation has been described at the tumour level in epithelial ovarian cancers (EOCs). Here, we report the identification of APC germline pathogenic variants in two patients diagnosed with premenopausal EOC in early 30s, with no other pathogenic variant detected in the known ovarian cancer predisposing genes. Subsequent tumour analysis showed neither a second hit of APC inactivation nor β-catenin activation. Both tumours did not have a homologous recombination (HR) deficiency, pointing towards the implication of other genes than those involved in HR. APC may contribute to the carcinogenesis of EOC in a multifactorial context. Further studies are required to clarify the role of APC in predisposition to EOC.

Keywords: Genetics.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Carcinoma, Ovarian Epithelial* / genetics
  • Female
  • Genes, APC*
  • Genetic Predisposition to Disease / genetics
  • Germ Cells / pathology
  • Germ-Line Mutation / genetics
  • Humans
  • Ovarian Neoplasms* / genetics
  • Premenopause
  • beta Catenin / genetics

Substances

  • APC protein, human
  • beta Catenin