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

Abstract

AbstractAPCgermline 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.APCinactivation has been described at the tumour level in epithelial ovarian cancers (EOCs). Here, we report the identification ofAPCgermline 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 ofAPCinactivation 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.APCmay contribute to the carcinogenesis of EOC in a multifactorial context. Further studies are required to clarify the role ofAPCin predisposition to EOC.