{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:37:14Z","timestamp":1792831034340,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Melanoma is a high\u2010tumor\u2010mutational\u2010burden (TMB) cancer, largely driven by ultraviolet\u2010induced DNA damage. Although TMB predicts response to immune checkpoint inhibitors (ICIs), the genomic factors underlying its variability remain unclear. In addition to canonical DNA\u2010repair defects such as mismatch repair (MMR) and POLE\/POLD1 mutations, alterations in chromatin regulators (CRs) may influence genome stability and mutational load. We analyzed melanoma cohorts from the MSK\u2010ICI, TCGA, MSK\u2010Met, DFCI, and UCLA datasets. TMB was compared between CR\u2010mutant and CR\u2013wild\u2010type tumors and overall cohorts, along with gene\u2010level analyses of individual CRs. Associations between the number of CR mutations and TMB were assessed. Overall survival (OS) in ICI\u2010treated patients was evaluated using Kaplan\u2013Meier and Cox models, with TCGA as a non\u2013ICI\u2010treated comparator. Across datasets, CR\u2010mutant melanomas consistently exhibited significantly higher TMB than CR\u2013wild\u2010type tumors. Several CRs were linked to elevated TMB, comparable to MMR\u2010 or POLE\/POLD1\u2010mutant tumors. Multiple CR alterations showed a positive linear relationship with TMB. In ICI\u2010treated cohorts, CR\u2010mutant tumors had significantly longer OS, while this link was not observed in non\u2013ICI\u2010treated cases. These findings suggest that CR mutations define a subset of melanomas with high TMB and improved response to ICIs, warranting prospective validation as predictive biomarkers.<\/jats:p>","DOI":"10.1111\/pcmr.70130","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:55:08Z","timestamp":1792828508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutations in Chromatin Regulator Genes Associate With\n                    <scp>TMB<\/scp>\n                    and Immunotherapy Response in Melanoma"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-9598","authenticated-orcid":false,"given":"Marija","family":"Gjorgjievska","sequence":"first","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1522-0678","authenticated-orcid":false,"given":"Djansel","family":"Bukovec","sequence":"additional","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andzelka","family":"Ilieva","sequence":"additional","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"},{"name":"Faculty of Medical Sciences Goce Delcev University  Stip North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3176-8856","authenticated-orcid":false,"given":"Milan","family":"Risteski","sequence":"additional","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Kungulovski","sequence":"additional","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"},{"name":"Fingerprint Diagnostics LLC  Skopje Republic of Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zan","family":"Mitrev","sequence":"additional","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7193-0964","authenticated-orcid":false,"given":"Aimilios","family":"Lallas","sequence":"additional","affiliation":[{"name":"Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6673-1795","authenticated-orcid":false,"given":"Goran","family":"Kungulovski","sequence":"additional","affiliation":[{"name":"Zan Mitrev Clinic  Skopje Republic of Macedonia"},{"name":"Fingerprint Diagnostics LLC  Skopje Republic of Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201012\u20100095"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.02.023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106490"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.12.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31345"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010025\u201002038\u20100"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.02.065"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102021\u2010002797"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041106"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdr2.70007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100654\u20105"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010022\u201002422\u20101"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010025\u201001003\u20107"},{"key":"e_1_2_9_18_1","unstructured":"National Cancer Institute.SEER Cancer Stat Facts: Melanoma of the Skin. Surveillance Epidemiology and End Results (SEER) Program [Internet].https:\/\/seer.cancer.gov\/statfacts\/html\/melan.html."},{"key":"e_1_2_9_19_1","volume-title":"StatPearls","author":"Puckett Y.","year":"2025"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010018\u20100312\u20108"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00951"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3486"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010021\u201009960\u20108"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333"}],"container-title":["Pigment Cell &amp; Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.70130","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pcmr.70130","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.70130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:55:09Z","timestamp":1792828509000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.70130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,24]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/pcmr.70130"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.70130","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,24]]},"assertion":[{"value":"2026-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70130"}}