Germline mutations of inhibins in early-onset ovarian epithelial tumors.

Autor: Tournier I; Inserm U1079, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, Cancéropôle Nord-Ouest, France., Marlin R, Walton K, Charbonnier F, Coutant S, Théry JC, Charbonnier C, Spurrell C, Vezain M, Ippolito L, Bougeard G, Roman H, Tinat J, Sabourin JC, Stoppa-Lyonnet D, Caron O, Bressac-de Paillerets B, Vaur D, King MC, Harrison C, Frebourg T
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2014 Mar; Vol. 35 (3), pp. 294-7. Date of Electronic Publication: 2013 Dec 27.
DOI: 10.1002/humu.22489
Abstrakt: 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.
(© 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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