Hong YY, Shou CH, Yang WL, Wang XD, Zhang Q, Liu XS, Yu JR. FGFR2 fusions as novel oncogenic drivers in gastrointestinal stromal tumors: Two case reports and review of literature. World J Gastrointest Oncol 2025; 17(11): 113262 [DOI: 10.4251/wjgo.v17.i11.113262]
Corresponding Author of This Article
Ji-Ren Yu, PhD, Professor, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China. yujr0909@zju.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Nov 15, 2025 (publication date) through Nov 13, 2025
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Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Oncology
ISSN
1948-5204
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Hong YY, Shou CH, Yang WL, Wang XD, Zhang Q, Liu XS, Yu JR. FGFR2 fusions as novel oncogenic drivers in gastrointestinal stromal tumors: Two case reports and review of literature. World J Gastrointest Oncol 2025; 17(11): 113262 [DOI: 10.4251/wjgo.v17.i11.113262]
Yan-Yun Hong, Chun-Hui Shou, Wei-Li Yang, Xiao-Dong Wang, Qing Zhang, Xiao-Sun Liu, Ji-Ren Yu, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Author contributions: Hong YY, Shou CH, Zhang Q, and Yu JR conceived and designed the study; Wang XD, Zhang Q, and Yang WL performed the procedures; Hong YY, Shou CH, and Zhang Q collected the data; Hong YY, Shou CH, Liu XS, and Yu JR analyzed and interpreted the data; Hong YY, Shou CH, Liu XS, and Yu JR wrote the manuscript; all authors have read and approved the final manuscript.
Informed consent statement: Owing to this study’s retrospective nature and minimal risks, the requirement for written informed consent was waived. The authors thank the patients’ family members for their cooperation and regular follow-ups.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ji-Ren Yu, PhD, Professor, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China. yujr0909@zju.edu.cn
Received: August 21, 2025 Revised: September 21, 2025 Accepted: October 9, 2025 Published online: November 15, 2025 Processing time: 85 Days and 8.7 Hours
Abstract
BACKGROUND
Gastrointestinal stromal tumors (GISTs) are generally characterized by driver mutations in KIT or PDGFRA. However, the molecular landscape of wild-type GISTs remains complex, posing significant therapeutic challenges. Recent evidence has indicated alterations in FGFR2 as potential oncogenic drivers in patients with various cancers. However, the role of these drivers in GIST pathogenesis remains underexplored.
CASE SUMMARY
We retrospectively evaluated two patients with GIST, diagnosed between August 2021 and July 2022, harboring FGFR2 mutations through hybrid capture-based next-generation sequencing (NGS). We analyzed their clinicopathological characteristics, treatment response, and long-term follow-up data. Both patients, a 47-year-old man (case 1) and a 43-year-old woman (case 2), underwent successful surgical resection and received adjuvant imatinib therapy. They achieved sustained remission with a median follow-up of 28 months. Notably, the NGS revealed novel FGFR2 rearrangements, an FGFR2-CIT/intergenic-FGFR2 fusion in case 1 and FGFR2-CAMK2G/FGFR2-VCL fusions in case 2 without canonical KIT or PDGFRA mutations. Both patients exhibited a favorable response to standard imatinib treatment.
CONCLUSION
Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.
Core Tip: Herein, we report, for the first time, novel FGFR2 rearrangements FGFR2-CIT/intergenic-FGFR2 and FGFR2-CAMK2G/FGFR2-VCL fusions as potential primary oncogenic drivers in two patients with KIT/PDGFRA wild-type gastrointestinal stromal tumors (GISTs). Both patients achieved sustained remission following adjuvant imatinib, challenging the notion that non-canonical alterations preclude tyrosine kinase inhibitor response. These findings might expand the molecular spectrum of GISTs and suggest that FGFR2 fusions might define a distinct subtype with potential sensitivity to FGFR-targeted therapies, offering new avenues for precision treatment in imatinib-resistant or advanced disease cases.
