ArticleGynecologic oncology2016
The mutational spectrum of FOXA2 in endometrioid endometrial cancer points to a tumor suppressor role.
Article in Gynecologic oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Association of MGMT promoter methylation with tumorigenesis features in patients with ovarian cancer: A systematic meta-analysis.Molecular genetics & genomic medicine · 2018Pooled it
- Comprehensive molecular characterization identifies therapeutic vulnerabilities in ovarian clear cell carcinoma.Genome medicine · 2026Article
- FOXA2 in cancer: from fundamental biology to clinical translation.Frontiers in oncology · 2026Review
- ACAT2 negatively modulated by FOXA2 suppresses ferroptosis to expedite the aggressive phenotypes of endometrial cancer cells.Histology and histopathology · 2025Article
- FOXA2 loss results in an increase of endometriosis development and LIF reveals a therapeutic effect for endometriosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- FOXA2 suppresses endometrial carcinogenesis and epithelial-mesenchymal transition by regulating enhancer activity.The Journal of clinical investigation · 2022Article
- A compendium of mutational cancer driver genes.Nature reviews. Cancer · 2020Review
- Integrative analysis of the forkhead box A2 (FOXA2) cistrome for the human endometrium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The long noncoding RNA Falcor regulates Foxa2 expression to maintain lung epithelial homeostasis and promote regeneration.Genes & development · 2019Article
- Ovarian insufficiency and CTNNB1 mutations drive malignant transformation of endometrial hyperplasia with altered PTEN/PI3K activities.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Functional characterization of recurrent FOXA2 mutations seen in endometrial cancers.International journal of cancer · 2018Article
- Generation of Mouse for Conditional Expression of Forkhead Box A2.Endocrinology · 2018Article
- The FOXA2 transcription factor is frequently somatically mutated in uterine carcinosarcomas and carcinomas.Cancer · 2018Article
- Forkhead box a2 (FOXA2) is essential for uterine function and fertility.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundForkhead box protein A2 (FOXA2) plays an important in development, cellular metabolism and tumorigenesis. The Cancer Genome Atlas (TCGA) identified a modest frequency of FOXA2 mutations in endometrioid endometrial cancers (EEC). The current study sought to determine the relationship between FOXA2 mutation and clinicopathologic features in EEC and FOXA2 expression.
methodsPolymerase chain reaction (PCR) amplification and sequencing were used to identify mutations in 542 EEC. Western blot, quantitative reverse transcriptase PCR (qRT-PCR) and immunohistochemistry (IHC) were used to assess expression. Methylation analysis was performed using combined bisulfite restriction analysis (COBRA) and sequencing. Chi-squared, Fisher's exact, Student's t- and log-rank tests were performed.
resultsFifty-one mutations were identified in 49 tumors (9.4% mutation rate). The majority of mutations were novel, loss of function (LOF) (78.4%) mutations, and most disrupted the DNA-binding domain (58.8%). Six recurrent mutations were identified. Only two tumors had two mutations and there was no evidence for FOXA2 allelic loss. Mutation status was associated with tumor grade and not associated with survival outcomes. Methylation of the FOXA2 promoter region was highly variable. Most tumors expressed FOXA2 at both the mRNA and protein level. In those tumors with mutations, the majority of cases expressed both alleles.
conclusionFOXA2 is frequently mutated in EEC. The pattern of FOXA2 mutations and expression in tumors suggests complex regulation and a haploinsufficient or dominant-negative tumor suppressor function. In vitro studies may shed light on how mutations in FOXA2 affect FOXA2 pioneer and/or transcription factor functions in EEC.
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