ArticleCancer research2022
FOXR2 Is an Epigenetically Regulated Pan-Cancer Oncogene That Activates ETS Transcriptional Circuits.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
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- Finding a brush when you expect a broom: a novel model of paediatric Wilms tumour evolution.Nature reviews. Urology · 2026Article
- FOXR2-activated CNS neuroblastoma: Characterized by variable structural disruption of theNeuro-oncology pediatrics · 2026Article
- Cigarette smoking combines with genetic variants to regulate FOXN3 and associate with bladder cancer risk.Archives of toxicology · 2026Article
- Targeting menin in lysine methyltransferase 2A/nucleophosmin-mutated leukemia: A novel strategy from epigenetic dysregulation to clinical therapy (Review).Oncology letters · 2025Review
- FOXR2 activation is not exclusive of CNS neuroblastoma.Neuro-oncology · 2025Article
- Aggressive Malignant Ossifying Fibromyxoid Tumor With a RareInternational journal of surgical pathology · 2025Review
- High resolution clonal architecture of hypomutated Wilms tumours.Nature communications · 2025Article
- FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma.Cancer research · 2025Article
- FOXR2 in cancer development: emerging player and therapeutic opportunities.Oncology research · 2025Review
- Defining neuroblastoma: From origin to precision medicine.Neuro-oncology · 2024Review
- Developmental origins shape the paediatric cancer genome.Nature reviews. Cancer · 2024Review
- Pan-cancer analyses reveal multi-omic signatures and clinical implementations of the forkhead-box gene family.Cancer medicine · 2023Article
- Expanding the molecular signatures of malignant ossifying fibromyxoid tumours with two novel gene fusions: PHF1::FOXR1 and PHF1::FOXR2.Histopathology · 2023Article
- A human embryonic stem cell-based model reveals the cell of origin of FOXR2-activated CNS neuroblastoma.Neuro-oncology advancesArticle
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49 authors at 14 institutions in 4 countries.
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Abstract
Forkhead box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly expressed FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for FOXR2 expression and proliferation in FOXR2-expressing cancer cells. FOXR2 promoted tumor growth across multiple cancer lineages and co-opted ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as a potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of hijacking of ETS transcription circuits by FOXR2 extends the mechanisms known to active ETS transcription factors and highlights how transcription factor families cooperate to enhance tumorigenesis. SIGNIFICANCE: This work identifies a novel promoter that drives aberrant FOXR2 expression and delineates FOXR2 as a pan-cancer oncogene that specifically activates ETS transcriptional circuits across human cancers. See related commentary by Liu and Northcott, p. 2977.
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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.