title: Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors.
abstract: Granulosa cell tumors (GCT) are unique sex-cord stromal tumors which account for ∼ 8% of all ovarian malignancies. They exhibit morphological, biochemical and hormonal features similar to proliferating granulosa cells of the preovulatory follicle, including estrogen and inhibin synthesis. A somatic missense mutation in the forkhead box L2 (FOXL2) gene (C134W) is unique to adult GCT, and absent in other ovarian cancers. FOXL2 is a transcription factor that plays a critical role in ovarian function, in particular, proliferation and differentiation of granulosa cells. The molecular mechanisms underlying the pathogenicity of the mutant FOXL2 remain unresolved. Here we review the molecular alterations known to be associated with mutant FOXL2 and the potential signaling implications. Several studies suggest that dysregulated FOXL2 function may alter cell cycle progression and apoptosis. Further insights into the molecular mechanism of GCT pathophysiology may identify therapeutic targets for the treatment of these tumors.
authors.affiliation: Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, VIC 3168, Australia; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Bldg. 77, 23 Innovation Walk, Clayton, VIC 3168, Australia. Electronic address: dilys.leung@hudson.org.au.
authors.forename: Dilys T H
authors.initials: DTH
authors.lastname: Leung
authors.affiliation: Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, VIC 3168, Australia. Electronic address: peter.fuller@hudson.org.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.affiliation: Hudson Institute of Medical Research, 27-31 Wright Street, Clayton, VIC 3168, Australia. Electronic address: simon.chu@hudson.org.au.
authors.forename: Simon
authors.initials: S
authors.lastname: Chu
mesh_terms: D000818:Animals; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006106:Granulosa Cell Tumor / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D009154:Mutation; D006080:Ovarian Follicle / Q000254:growth & development
chemical_list: D051858:Forkhead Transcription Factors
keywords: FOXL2; Granulosa cell tumor; Ovarian cancer; Ovary