Germline mutations of inhibins in early-onset ovarian epithelial tumors.
Hum Mutat
; 35(3): 294-7, 2014 Mar.
Article
in En
| MEDLINE
| ID: mdl-24302632
ABSTRACT
To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the ßA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the ßA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Germ-Line Mutation
/
Neoplasms, Glandular and Epithelial
/
Inhibin-beta Subunits
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
Language:
En
Year:
2014
Type:
Article