{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:44:32Z","timestamp":1791895472236,"version":"4.3.4"},"reference-count":28,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["MFAG 2019"],"award-info":[{"award-number":["MFAG 2019"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["22940"],"award-info":[{"award-number":["22940"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["CUP H83C22000550006"],"award-info":[{"award-number":["CUP H83C22000550006"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007886","name":"Dana-Farber Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["annalsofoncology.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Annals of Oncology"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.annonc.2025.06.003","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T20:00:47Z","timestamp":1750276847000},"page":"1132-1141","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["DNA methyltransferase 3A (DNMT3A) mutations and PD-(L)1 blockade efficacy in non-small-cell lung cancer"],"prefix":"10.1016","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-2678","authenticated-orcid":false,"given":"B.","family":"Ricciuti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-5917","authenticated-orcid":false,"given":"S.","family":"Scalera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-1105","authenticated-orcid":false,"given":"X.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Elkrief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tagliamento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1665-3367","authenticated-orcid":false,"given":"E.","family":"Gariazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Paoloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.G.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Pecci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8877-4315","authenticated-orcid":false,"given":"A.","family":"Di Federico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Santo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.V.","family":"Alessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Aldea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2394-9895","authenticated-orcid":false,"given":"E.","family":"Garbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lamberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-6821","authenticated-orcid":false,"given":"W.","family":"Zrafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.B.","family":"Micol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-9735","authenticated-orcid":false,"given":"L.M.","family":"Sholl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Cappuzzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2721-4888","authenticated-orcid":false,"given":"N.","family":"Calonaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Caravagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Besse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Schoenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maugeri-Sacca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.M.","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.annonc.2025.06.003_bib1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1200\/JCO.22.01990","article-title":"Pembrolizumab plus chemotherapy in squamous non\u2013small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study","volume":"41","author":"Novello","year":"2023","journal-title":"J Clin Oncol"},{"issue":"21","key":"10.1016\/j.annonc.2025.06.003_bib2","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1056\/NEJMoa1810865","article-title":"Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer","volume":"379","author":"Paz-Ares","year":"2018","journal-title":"N Engl J Med"},{"issue":"19","key":"10.1016\/j.annonc.2025.06.003_bib3","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"issue":"24","key":"10.1016\/j.annonc.2025.06.003_bib4","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1056\/NEJMoa1716948","article-title":"Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC","volume":"378","author":"Socinski","year":"2018","journal-title":"N Engl J Med"},{"issue":"2","key":"10.1016\/j.annonc.2025.06.003_bib5","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S1470-2045(20)30641-0","article-title":"First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial","volume":"22","author":"Paz-Ares","year":"2021","journal-title":"Lancet Oncol"},{"issue":"12","key":"10.1016\/j.annonc.2025.06.003_bib6","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.jtho.2022.09.109","article-title":"Predictive biomarkers for immunotherapy in lung cancer: perspective from the International Association for the Study of Lung Cancer Pathology Committee","volume":"17","author":"Mino-Kenudson","year":"2022","journal-title":"J Thorac Oncol"},{"issue":"12","key":"10.1016\/j.annonc.2025.06.003_bib7","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/s41416-022-01743-4","article-title":"Biomarkers of response to PD-1 pathway blockade","volume":"126","author":"Li","year":"2022","journal-title":"Br J Cancer"},{"issue":"1","key":"10.1016\/j.annonc.2025.06.003_bib8","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3390\/biomedicines11010169","article-title":"Targeting epigenetic mechanisms: a boon for cancer immunotherapy","volume":"11","author":"Parab","year":"2023","journal-title":"Biomedicines"},{"issue":"1","key":"10.1016\/j.annonc.2025.06.003_bib9","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41467-017-02630-w","article-title":"DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer","volume":"9","author":"Luo","year":"2018","journal-title":"Nat Commun"},{"issue":"44","key":"10.1016\/j.annonc.2025.06.003_bib10","doi-asserted-by":"crossref","first-page":"18061","DOI":"10.1073\/pnas.1114946108","article-title":"Deletion of the de novo DNA methyltransferase Dnmt3a promotes lung tumor progression","volume":"108","author":"Gao","year":"2011","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"10.1016\/j.annonc.2025.06.003_bib11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nrc3895","article-title":"DNMT3A in haematological malignancies","volume":"15","author":"Yang","year":"2015","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"10.1016\/j.annonc.2025.06.003_bib12","doi-asserted-by":"crossref","first-page":"751","DOI":"10.5858\/arpa.2016-0527-OA","article-title":"Validation of OncoPanel a targeted next-generation sequencing assay for the detection of somatic variants in cancer","volume":"141","author":"Garcia","year":"2017","journal-title":"Arch Pathol Lab Med"},{"issue":"3","key":"10.1016\/j.annonc.2025.06.003_bib13","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jmoldx.2014.12.006","article-title":"Memorial Sloan Kettering-integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology","volume":"17","author":"Cheng","year":"2015","journal-title":"J Mol Diagn"},{"issue":"3","key":"10.1016\/j.annonc.2025.06.003_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0264138","article-title":"Clinical and analytical validation of FoundationOne\u00aeCDx, a comprehensive genomic profiling assay for solid tumors","volume":"17","author":"Milbury","year":"2022","journal-title":"PLoS One"},{"key":"10.1016\/j.annonc.2025.06.003_bib15","article-title":"Harmonization of tumor mutational burden quantification and association with response to immune checkpoint blockade in non\u2013small-cell lung cancer","volume":"3","author":"Vokes","year":"2019","journal-title":"JCO Precis Oncol"},{"issue":"4","key":"10.1016\/j.annonc.2025.06.003_bib16","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"issue":"17","key":"10.1016\/j.annonc.2025.06.003_bib17","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkr407","article-title":"Predicting the functional impact of protein mutations: application to cancer genomics","volume":"39","author":"Reva","year":"2011","journal-title":"Nucleic Acids Res"},{"issue":"13","key":"10.1016\/j.annonc.2025.06.003_bib18","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"issue":"23","key":"10.1016\/j.annonc.2025.06.003_bib19","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V126.23.4106.4106","article-title":"Age-associated acquired mutations in hematopoietic cells predominantly affect epigenetic regulators TET2 and DNMT3A and are associated with distinct biological and hematological profiles","volume":"126","author":"Buscarlet","year":"2015","journal-title":"Blood"},{"issue":"12","key":"10.1016\/j.annonc.2025.06.003_bib20","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1182\/bloodadvances.2022006968","article-title":"Cell origin\u2013dependent cooperativity of mutant Dnmt3a and Npm1 in clonal hematopoiesis and myeloid malignancy","volume":"6","author":"SanMiguel","year":"2022","journal-title":"Blood Adv"},{"key":"10.1016\/j.annonc.2025.06.003_bib21","article-title":"Clonal hematopoiesis: updates and implications at the solid tumor-immune interface","volume":"7","author":"Buttigieg","year":"2023","journal-title":"JCO Precis Oncol"},{"issue":"3","key":"10.1016\/j.annonc.2025.06.003_bib22","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.annonc.2022.12.002","article-title":"Clonal KEAP1 mutations with loss of heterozygosity share reduced immunotherapy efficacy and low immune cell infiltration in lung adenocarcinoma","volume":"34","author":"Scalera","year":"2023","journal-title":"Ann Oncol"},{"issue":"7","key":"10.1016\/j.annonc.2025.06.003_bib23","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: islands, start sites, gene bodies and beyond","volume":"13","author":"Jones","year":"2012","journal-title":"Nat Rev Genet"},{"issue":"1","key":"10.1016\/j.annonc.2025.06.003_bib24","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s42003-022-03843-6","article-title":"Reversible epigenetic alterations regulate class I HLA loss in prostate cancer","volume":"5","author":"Rodems","year":"2022","journal-title":"Commun Biol"},{"issue":"11","key":"10.1016\/j.annonc.2025.06.003_bib25","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tig.2021.05.002","article-title":"Navigating the DNA methylation landscape of cancer","volume":"37","author":"Nishiyama","year":"2021","journal-title":"Trends Genet"},{"issue":"4","key":"10.1016\/j.annonc.2025.06.003_bib26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41416-024-02772-x","article-title":"KDM1A, a potent and selective target, for the treatment of DNMT3A-deficient non-small cell lung cancer","volume":"131","author":"Zhao","year":"2024","journal-title":"Br J Cancer"},{"issue":"10","key":"10.1016\/j.annonc.2025.06.003_bib27","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/s43018-021-00271-z","article-title":"The next generation of DNMT inhibitors","volume":"2","author":"Mehdipour","year":"2021","journal-title":"Nat Cancer"},{"issue":"1","key":"10.1016\/j.annonc.2025.06.003_bib28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s13148-021-01154-x","article-title":"DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application","volume":"13","author":"Hu","year":"2021","journal-title":"Clin Epigenetics"}],"container-title":["Annals of Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S092375342500804X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S092375342500804X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:21:38Z","timestamp":1790817698000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S092375342500804X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S092375342500804X"],"URL":"https:\/\/doi.org\/10.1016\/j.annonc.2025.06.003","relation":{},"ISSN":["0923-7534"],"issn-type":[{"value":"0923-7534","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"DNA methyltransferase 3A (DNMT3A) mutations and PD-(L)1 blockade efficacy in non-small-cell lung cancer","name":"articletitle","label":"Article Title"},{"value":"Annals of Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.annonc.2025.06.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 European Society for Medical Oncology. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}