ArticleJournal of the National Cancer Institute2021
Germline MBD4 Mutations and Predisposition to Uveal Melanoma.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- GWAS meta-analysis provides new insights into uveal melanoma risk.British journal of cancer · 2026Pooled it
- Uveal melanoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up.ESMO open · 2026Guideline
- Survival of Patients With MBD4-Mutated Metastatic Uveal Melanoma Treated With Immune Checkpoint Inhibitors.Translational vision science & technology · 2026Article
- Impact of Multigene Panel Testing in High-Risk Uveal Melanoma Patients.Pigment cell & melanoma research · 2026Article
- Biallelic germline MBD4 mutations predispose to colorectal polyposis, hypermutated AML, and schwannomas.Familial cancer · 2026Article
- Paediatric uveal melanoma in Ireland 2010 - 2024: incidence, clinical features, management, and outcomes.Eye (London, England) · 2026Article
- Rare Germline Variants in CDKN2A-Negative Children and Adolescents With Cutaneous Melanoma.Pigment cell & melanoma research · 2026Article
- Mbd4 and MutSα protect cells from spontaneous deamination of 5-methylcytosine.Nucleic acids research · 2026Article
- Germline Cancer Susceptibility Variants in Patients With Uveal Melanoma.Pigment cell & melanoma research · 2025Article
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Short Report: The Variants inJournal of clinical medicine · 2025Article
- Genetics, genomics and clinical features of adenomatous polyposis.Familial cancer · 2025Review
- Pathogenic Germline Variants in Uveal Melanoma Driver and BAP1-Associated Genes in Finnish Patients with Uveal Melanoma.Pigment cell & melanoma research · 2025Article
- Identification of new candidate genes for the hereditary predisposition to uveal melanoma: IGCMU trial.Frontiers in oncology · 2025Article
- Factors associated with time until metastatic spread in patients with primary uveal melanoma: A retrospective analysis.PloS one · 2025Article
- Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes.Nature communications · 2024Article
- Bilateral Uveal Melanoma: An Insight into Genetic Predisposition in Four New Unrelated Patients and Review of Published Cases.Journal of clinical medicine · 2024Article
- GermlineGenes · 2024Review
- A naturally occurring variant ofGenome research · 2023Article
- Additional primary malignancies in a Polish cohort of uveal melanoma patients: a review of 644 patients with long-term follow-up.BMC ophthalmology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUveal melanoma (UM) arises from malignant transformation of melanocytes in the uveal tract of the eye. This rare tumor has a poor outcome with frequent chemo-resistant liver metastases. BAP1 is the only known predisposing gene for UM. UMs are generally characterized by low tumor mutation burden, but some UMs display a high level of CpG>TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1093 primary UM case patients and a series of 192 UM tumors with monosomy 3 (M3).
methodsWe performed MBD4 targeted sequencing on pooled germline (n = 1093) and tumor (n = 192) DNA samples of UM patients. MBD4 variants (n = 28) were validated by Sanger sequencing. We performed whole-exome sequencing on available tumor samples harboring MBD4 variants (n = 9). Variants of unknown pathogenicity were further functionally assessed.
resultsWe identified 8 deleterious MBD4 mutations in the consecutive UM series, a 9.15-fold (95% confidence interval = 4.24-fold to 19.73-fold) increased incidence compared with the general population (Fisher exact test, P = 2.00 × 10-5, 2-sided), and 4 additional deleterious MBD4 mutations in the M3 cohort, including 3 germline and 1 somatic mutations. Tumors carrying deleterious MBD4 mutations were all associated with high tumor mutation burden and a CpG>TpG hypermutator phenotype.
conclusionsWe demonstrate that MBD4 is a new predisposing gene for UM associated with hypermutated M3 tumors. The tumor spectrum of this predisposing condition will likely expand with the addition of MBD4 to diagnostic panels. Tumors arising in such a context should be recognized because they may respond to immunotherapy.
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