{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:21:46Z","timestamp":1787559706806,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"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":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    HER2\u2010mutant non\u2010small cell lung cancer (NSCLC) comprises molecularly heterogeneous tumors with diverse ERBB2 mutation subtypes, and HER2\u2010directed therapies have increased the need for refined molecular stratification. However, subtype\u2010specific co\u2010occurring genomic alterations remain incompletely characterized. We performed a two\u2010stage clinicogenomic analysis to identify and validate recurrent co\u2010mutations in HER2\u2010mutant NSCLC. A public MSK\u2010IMPACT lung adenocarcinoma cohort was used for discovery, and a nationwide Japanese real\u2010world cohort from the Center for Cancer Genomics and Advanced Therapeutics was used for validation. In the MSK\u2010IMPACT cohort of 2201 lung adenocarcinomas, TERT mutations were significantly enriched in ERBB2\u2010mutant tumors compared with ERBB2\u2010wild\u2010type tumors (odds ratio, 2.40; 95% confidence interval, 1.12\u20134.70;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.017). This association was reproduced in the independent validation cohort, where 16 of 174 HER2\u2010mutant NSCLC cases harbored concurrent TERT mutations, all of which were promoter\u2010region variants. Among the evaluated clinicogenomic variables, the ERBB2 mutation subtype was the only factor significantly associated with TERT mutation status. The ERBB2 G776\u2010altered subtype remained independently associated with TERT mutation after multivariable adjustment (adjusted odds ratio, 7.49; 95% confidence interval, 1.81\u201331.0;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006). In a small exploratory subset of trastuzumab deruxtecan\u2010treated patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200952; TERT\u2010mutated,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095), no statistically robust differences in treatment outcomes were observed according to TERT mutation status. TERT promoter mutations are recurrent co\u2010mutations in HER2\u2010mutant NSCLC and are preferentially associated with the ERBB2 G776\u2010altered subgroup. These findings support ERBB2 subtype\u2010aware molecular stratification and highlight previously underappreciated genomic heterogeneity within HER2\u2010mutant NSCLC.\n                  <\/jats:p>","DOI":"10.1111\/cas.70504","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:11:31Z","timestamp":1786615891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TERT<\/scp>\n                    Promoter Mutations Are Preferentially Associated With the\n                    <scp>ERBB2 G776<\/scp>\n                    \u2010Altered Subtype of\n                    <scp>HER2<\/scp>\n                    \u2010Mutant\n                    <scp>NSCLC<\/scp>"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-2110","authenticated-orcid":false,"given":"Akihiro","family":"Yoshimura","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"},{"name":"Department of Respiratory Medicine Japanese Red Cross Society Kyoto Daiichi Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juichiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Japanese Red Cross Society Kyoto Daiichi Hospital  Kyoto Japan"},{"name":"Department of Clinical Oncology Japanese Red Cross Society Kyoto Daiichi Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Takumi","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Japanese Red Cross Society Kyoto Daiichi Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.45.3753"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010021\u201002089\u2010z"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv573"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2218\u20106751.2014.02.06"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112431"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2503704"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019\u20100547"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1121708"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201017\u20101841"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201014\u20101236"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010024\u201000720\u20109"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/CCI.20.00108"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201022\u20100417"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201006454\u20107"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428\u2010014\u20101608\u20104"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2014.10.009"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab0015"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.01.020"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.806737"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1229259"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201021\u20100201"}],"container-title":["Cancer 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