{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:11:59Z","timestamp":1789841519458,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871990"],"award-info":[{"award-number":["81871990"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Project in 14th Five-Year Plan Special for Cancer Prevention"},{"name":"Treatment Research from Tianjin Cancer Institute"},{"name":"Construction Project of Cancer Precision Diagnosis"},{"name":"Drug Treatment Technology from TUCIH","award":["ZLJZZDYYWZL13"],"award-info":[{"award-number":["ZLJZZDYYWZL13"]}]},{"name":"Tianjin Key Medical Discipline (Pathology) Construction Project","award":["TJYXZDXK-012A"],"award-info":[{"award-number":["TJYXZDXK-012A"]}]},{"name":"Scientific Research Project from Tianjin Education Commission","award":["2022KJ217"],"award-info":[{"award-number":["2022KJ217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Although there have been multiple lines of drugs for gastrointestinal stromal tumors (GISTs), the drug response depends on the progressive tumors\u2019 biological behaviors and secondary mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated the primary and secondary mutations in multiple tumors from the same patients and at multiple regions from the same tumor to analyze the inter- and intratumoral heterogeneities using Sanger sequencing and next-generation sequencing (NGS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Secondary mutations were more frequently detected in patients with a targeted therapy history and who continued their targeted therapy until surgery or biopsy, in larger tumors, and in tumors located in the intestine, abdominal cavity, and mesentery. Secondary mutations were detected in only 57.5% of the samples from the cases with secondary mutations, and 34.8% of the cases presented multiple types of secondary mutations, including both intertumoral and intratumoral heterogeneities. Temporal heterogeneity was also observed at different time points of progression. The results of NGS and Sanger sequencing were consistent for the individual sample, but Sanger sequencing detected multiple types of secondary mutations from different tumors of the same patient. Liquid biopsy also only detected partial secondary mutations revealed by Sanger sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Progressive GISTs had intertumoral and intratumoral heterogeneities of secondary mutations. Sanger sequencing had its own advantage in revealing the heterogeneity of secondary mutations. The improvement in the detection rate of secondary mutations by selecting the appropriate tumor sample to be tested, or even the appropriate tumor region or test method, is helpful to identify the optimal drugs for progressive GISTs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf110","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T12:55:09Z","timestamp":1747400109000},"source":"Crossref","is-referenced-by-count":4,"title":["Clinicopathological characteristics of progressive gastrointestinal stromal tumors and heterogeneity analyses of secondary mutations"],"prefix":"10.1093","volume":"30","author":[{"given":"Jiaxin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8916-9598","authenticated-orcid":false,"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer , Tianjin 300060 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"2025052712351776900_CIT0001","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1002\/cncr.33630","article-title":"An updated review of the treatment landscape for advanced gastrointestinal stromal tumors","volume":"127","author":"Patel","year":"2021","journal-title":"Cancer"},{"key":"2025052712351776900_CIT0002","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev-pathol-042220-021510","article-title":"Molecular pathogenesis of gastrointestinal stromal tumor: a paradigm for personalized medicine","volume":"17","author":"Dermawan","year":"2022","journal-title":"Annu Rev Pathol"},{"key":"2025052712351776900_CIT0003","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41571-022-00606-4","article-title":"New treatment strategies for advanced-stage gastrointestinal stromal 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