ArticleThe journal of pathology. Clinical research2021
Adult-type granulosa cell tumor of the ovary: a FOXL2-centric disease.
Article in The journal of pathology. Clinical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The Prognostic Significance of Adjuvant Chemotherapy in Adult Ovarian Granulosa Cell Tumors: A Systematic Review and Meta-analysis.Cancer control : journal of the Moffitt Cancer CenterPooled it
- Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: the Greko II study (GETHI2013-01).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Trial
- Granulosa cell tumors and menopausal hormone therapy: A narrative review.Gynecologic oncology reports · 2026Review
- FGFR1 mutations identified in FOXL2-wild type ovarian adult granulosa cell tumors are not present in testicular counterparts: Re-analysis of a multi-institutional series.Virchows Archiv : an international journal of pathology · 2026Article
- Advances in non-germ cell tumours of the testis: focus on new molecular developments in sex cord-stromal tumours.Histopathology · 2026Review
- Article
- Granulosa Cells-Related MicroRNAs in Ovarian Diseases: Mechanism, Facts and Perspectives.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Molecular features for timely cancer diagnosis and treatment - tumors of the ovary, fallopian tube and endometrium.Virchows Archiv : an international journal of pathology · 2024Review
- Effectiveness of adjuvant systemic therapy following complete cytoreductive surgery in patients with recurrent granulosa cell tumours of the ovary.Scientific reports · 2024Article
- Article
- Clinical characteristics and oncological outcomes of recurrent adult granulosa cell tumor of ovary: A retrospective study of seventy patients.Acta obstetricia et gynecologica Scandinavica · 2023Article
- ERβ in Granulosa Cell Tumors and Its Clinical Potential.Endocrinology · 2023Review
- Immunohistochemical markers of prognosis in adult granulosa cell tumors of the ovary - a review.Journal of ovarian research · 2023Review
- Whole-exome sequencing reveals rare genetic variations in ovarian granulosa cell tumor.Bosnian journal of basic medical sciences · 2022Article
- Synchronous granulosa cell tumor of the ovary and endometrial adenocarcinoma.Journal of surgical case reports · 2022Article
- Analysis of Non-Relapsed and Relapsed Adult Type Granulosa Cell Tumors Suggests Stable Transcriptomes during Tumor Progression.Current issues in molecular biology · 2022Article
- Cytologic features of sex cord-stromal tumors in women.Cancer cytopathology · 2022Article
- Prevalence of predictive biomarkers in a large cohort of molecularly defined adult-type ovarian granulosa cell tumors.Gynecologic oncology · 2021Article
- Genomic alterations in gynecological malignancies: histotype-associated driver mutations, molecular subtyping schemes, and tumorigenic mechanisms.Journal of human genetics · 2021Review
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 5 countries.
Funding
Abstract
Adult-type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord-stromal tumors and 2-5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one-third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole-genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon-based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle-related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.