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Germline mutations of inhibins in early-onset ovarian epithelial tumors.
- Source :
-
Human mutation [Hum Mutat] 2014 Mar; Vol. 35 (3), pp. 294-7. Date of Electronic Publication: 2013 Dec 27. - Publication Year :
- 2014
-
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 βA-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 βA-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.<br /> (© 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.)
- Subjects :
- Activins biosynthesis
Carcinoma, Ovarian Epithelial
Cell Differentiation
Cohort Studies
Epithelial Cells metabolism
Exome
Female
Granulosa Cells metabolism
Humans
Inhibins biosynthesis
Sequence Analysis, DNA
Young Adult
Germ-Line Mutation
Inhibin-beta Subunits genetics
Neoplasms, Glandular and Epithelial genetics
Ovarian Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 24302632
- Full Text :
- https://doi.org/10.1002/humu.22489