{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:38:12Z","timestamp":1790753892583,"version":"4.1.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Programme de Recherche Translationnelle en Canc\u00e9rologie","award":["PRT-K19-51"],"award-info":[{"award-number":["PRT-K19-51"]}]},{"name":"Institut National du Cancer\u2014Direction g\u00e9n\u00e9rale de l\u2019Offre de soins"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Monoallelic germline MBD4 pathogenic variants were recently reported to cause a predisposition to uveal melanoma, associated with a specific tumor mutational signature and good response to immunotherapy. Monoallelic tumor pathogenic variants have also been described in brain tumors, breast cancers, and myxofibrosarcomas, whereas biallelic germline MBD4 pathogenic variants have been involved in a recessive hereditary adenomatous polyposis and a specific type of acute myeloid leukemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analyzed MBD4 for all patients with a diagnosis of uveal melanoma at Institut Curie since July 2021 and in the 3240 consecutive female probands explored at the Institut Curie for suspicion of predisposition to breast cancer between July 2021 and February 2023.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We describe 25 families whose probands carry a monoallelic germline pathogenic variant in MBD4. Eighteen of these families presented with uveal melanoma (including a case patient with multiple uveal melanoma), and 7 families presented with breast cancer. Family histories showed the first familial case of uveal melanoma in monoallelic MBD4 pathogenic variant carriers and other various types of cancers in relatives, especially breast, renal, and colorectal tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Monoallelic MBD4 pathogenic variant may explain some cases of familial and multiple uveal melanoma as well as various cancer types, expanding the tumor spectrum of this predisposition. Further genetic testing in relatives combined with molecular tumor analyses will help define the tumor spectrum and estimate each tumor\u2019s risk.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djad248","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T22:36:23Z","timestamp":1701988583000},"page":"580-587","source":"Crossref","is-referenced-by-count":22,"title":["Familial uveal melanoma and other tumors in 25 families with monoallelic germline <i>MBD4<\/i> variants"],"prefix":"10.1093","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5714-6612","authenticated-orcid":false,"given":"Marie-Charlotte","family":"Villy","sequence":"first","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9 , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Le Ven","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, France"},{"name":"Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Le Mentec","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Masliah-Planchon","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-5771","authenticated-orcid":false,"given":"Anne","family":"Vincent-Salomon","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Dubois d\u2019Enghien","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Piperno-Neumann","sequence":"additional","affiliation":[{"name":"Paris Sciences & Lettres Research University , Paris, France"},{"name":"Department of Medical Oncology, Institut Curie , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9721-777X","authenticated-orcid":false,"given":"Alexandre","family":"Matet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 , Paris, France"},{"name":"Department of Ocular Oncology, Institut Curie , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Malaise","sequence":"additional","affiliation":[{"name":"Paris Sciences & Lettres Research University , Paris, France"},{"name":"Department of Ocular Oncology, Institut Curie , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Bubien","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Bergoni\u00e9 , Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lortholary","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, GINECO-H\u00f4pital Priv\u00e9 du Confluent , Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Ait Omar","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, AP-HP, H\u00f4pital Avicenne , Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Cavaill\u00e9","sequence":"additional","affiliation":[{"name":"Department of Oncogenetics, Centre Jean Perrin, Universit\u00e9 Clermont Auvergne, INSERM, U1240 Imagerie Mol\u00e9culaire et Strat\u00e9gies Th\u00e9ranostiques, AURAGEN , Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Stoppa-Lyonnet","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9 , Paris, France"},{"name":"Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Cassoux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 , Paris, France"},{"name":"Department of Ocular Oncology, Institut Curie , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8100-2272","authenticated-orcid":false,"given":"Marc-Henri","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institut Curie , Paris, France"},{"name":"Paris Sciences & Lettres Research University , Paris, France"},{"name":"Inserm 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