{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T16:20:39Z","timestamp":1763828439922,"version":"3.45.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Chinese Medical Science and Technology Foundation","award":["2022ZA030"],"award-info":[{"award-number":["2022ZA030"]}]},{"name":"Zhejiang Medical and Health Technology Project","award":["2021KY582"],"award-info":[{"award-number":["2021KY582"]}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H160053"],"award-info":[{"award-number":["LY21H160053"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite the increasing approval and ongoing clinical trials of FGFR-targeted therapies, accurately detecting FGFR fusions remains a challenge due to limited research, low incidence rates, complex fusion partner distribution, and unique kinase domain distribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a multicenter study to comprehensively profile FGFR fusions in the largest Chinese pan-cancer cohort to date, comprising 118 FGFR fusions from 114 individuals. Both DNA- and RNA-based sequencing approaches were utilized to reveal novel and fundamental features of FGFR fusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our research reveals an incidence rate of 0.96% for FGFR rearrangements within this Chinese cohort, including a high incidence rate of FGFR fusions (40%) in parotid gland carcinoma. However, this is based on a small sample size of 5 tumors and should be interpreted cautiously pending validation in larger cohorts. We also uncovered distinct breakpoint distribution patterns across various FGFR rearrangements. For example, a primary breakpoint in intron17 of FGFR2 was predominant (21\/22), while FGFR1\/3 breakpoints displayed substantial diversity. For the first time, we identified \u201chot\u201d breakpoints in FGFR1 intron17, exon18, and FGFR3's 3\u2019 untranslated region. These findings underline the importance of incorporating these regions in targeted sequencing to ensure comprehensive detection of FGFR1\/3 fusions. Notably, we observed a predilection for intrachromosomal distribution in common FGFR1\/2\/3 fusions. In contrast, most novel fusions (12\/15) exhibited an interchromosomal distribution pattern, indicating variations in the fusion formation mechanism. Importantly, our study demonstrates the substantial incremental value of RNA-NGS or other orthogonal methods in confirming the functionality of FGFR rearrangements initially identified by DNA sequencing. In our cohort, 46% (6\/13) of rare FGFR1\/2\/3 fusions lacked detectable RNA transcripts; however, this does not definitively indicate non-functionality as factors such as low RNA quality, expression below detection limits, or nonsense-mediated decay may contribute. Therefore, RNA-based validation is critical for accurately identifying potentially targetable FGFR fusions and guiding therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings offer critical novel insights into functional FGFR fusions and bear considerable clinical implications for identifying individuals whose tumors are most likely to respond favorably to FGFR-targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf347","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:56:52Z","timestamp":1760183812000},"source":"Crossref","is-referenced-by-count":0,"title":["Illuminating the\n                    <i>FGFR<\/i>\n                    fusion landscape in Chinese patients: unveiling novel molecular insights and clinical implications"],"prefix":"10.1093","volume":"30","author":[{"given":"Zhuo","family":"Liu","sequence":"first","affiliation":[{"name":"Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , Hangzhou, Zhejiang 310022,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jilin Agriculture University College of Life Sciences, , Changchun 130118,","place":["China"]},{"name":"Jichenjunchuang Clinical Laboratory , Hangzhou 310000,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoming","family":"Wang","sequence":"additional","affiliation":[{"name":"Jichenjunchuang Clinical Laboratory , Hangzhou 310000,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyuan","family":"Qian","sequence":"additional","affiliation":[{"name":"General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital, Hangzhou Medical College) , Hangzhou 310014,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengchuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College , Hangzhou 310014,","place":["China"]},{"name":"Cancer Center, Clinical Research Center, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital, Hangzhou Medical College) , Hangzhou 310014,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Yang","sequence":"additional","affiliation":[{"name":"General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital, Hangzhou Medical College) , Hangzhou 310014,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhua","family":"Tao","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , Hangzhou, Zhejiang 310022,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanxi","family":"Shao","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , Hangzhou, Zhejiang 310022,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Lv","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , Hangzhou, Zhejiang 310022,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jichenjunchuang Clinical Laboratory , Hangzhou 310000,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hangzhou Cosmos Wisdom Biotechnology Co. 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