{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:54Z","timestamp":1788415974077,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Background<\/jats:title>\n \n ALK<\/jats:italic>\n fusions are validated oncogenic drivers, yet their molecular heterogeneity and therapeutic implications remain poorly characterized. This study defined the landscape of\n ALK<\/jats:italic>\n fusion partners,\n EML4-ALK<\/jats:italic>\n variants, and co-mutations and their impact on treatment responses in a large Chinese pan-cancer cohort.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We retrospectively analyzed 16,335 consecutive pan-cancer patients via next-generation sequencing to identify\n ALK<\/jats:italic>\n fusions. Clinical characteristics, fusion partners, co-mutations, and treatment responses were evaluated. Progression-free survival (PFS) was assessed in advanced non-small cell lung cancer (NSCLC) patients receiving first-line\n ALK<\/jats:italic>\n tyrosine kinase inhibitors (TKIs), stratified by\n EML4-ALK<\/jats:italic>\n variants and\n TP53<\/jats:italic>\n status.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n ALK<\/jats:italic>\n fusions were detected in 321 patients. NSCLC accounted for 93.1% (299\/321), predominantly adenocarcinomas (292\/299, 97.7%).\n EML4<\/jats:italic>\n was the predominant fusion partner, accounting for 92.1% of\n ALK<\/jats:italic>\n fusion in lung adenocarcinoma but only 27.3% in extrapulmonary tumors. Conversely, non-\n EML4<\/jats:italic>\n fusions were more frequent in extrapulmonary tumors (72.7%). Among 13 evaluable advanced-stage patients with rare\n ALK<\/jats:italic>\n fusions, 10 achieved objective response (76.9%). In 161 advanced or recurrent NSCLC patients treated with\n ALK<\/jats:italic>\n -TKIs, the median PFS was 28.2 months. Patients with long\n EML4-ALK<\/jats:italic>\n variants had superior PFS than those with short variants when treated with second-generation TKIs (55.7 vs. 27.1 months;\n p<\/jats:italic>\n \u00a0=\u00a00.019).\n TP53<\/jats:italic>\n co-mutations were associated with shorter PFS in the first-generation TKI subgroup (5.6 vs. 21.4 months;\n p<\/jats:italic>\n =\u00a00.009).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n While\n ALK<\/jats:italic>\n fusion partners exhibit tumor-type specificity,\n ALK<\/jats:italic>\n -TKIs demonstrate potential efficacy in rare fusions though these findings are exploratory and need validation. Short\n EML4-ALK<\/jats:italic>\n variants and\n TP53<\/jats:italic>\n co-mutation are associated with poorer TKI efficacy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1890263","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:17:06Z","timestamp":1788412626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of clinical features and outcomes in a Chinese cohort with ALK fusion across pan-cancer: a retrospective study"],"prefix":"10.3389","volume":"16","author":[{"given":"Meng","family":"Zhang","sequence":"first","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, 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Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meizhu","family":"Meng","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiying","family":"Ye","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziran","family":"Yang","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Ma","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmei","family":"Li","sequence":"additional","affiliation":[{"name":"Key laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital & Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqin","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of 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