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FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer |
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| Authors: | Hiroko Hasegawa Hiroya Taniguchi Yoshiaki Nakamura Takeshi Kato Satoshi Fujii Hiromichi Ebi Manabu Shiozawa Satoshi Yuki Toshiki Masuishi Ken Kato Naoki Izawa Toshikazu Moriwaki Eiji Oki Yoshinori Kagawa Tadamichi Denda Tomohiro Nishina Akihito Tsuji Hiroki Hara Taito Esaki Tomohiro Nishida Hisato Kawakami Yasutoshi Sakamoto Izumi Miki Wataru Okamoto Kentaro Yamazaki Takayuki Yoshino |
| Affiliation: | 1. Department of Gastroenterology and Hepatology, National Hospital Organization, Osaka National Hospital, Osaka, Japan;2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan;3. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan Translational Research Support Section, Clinical Research Support Department, National Cancer Center Hospital East, Kashiwa, Japan;4. Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan;5. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center East, Kashiwa, Japan;6. Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan;7. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan;8. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan;9. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan;10. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan;11. Division of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan;12. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan;13. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;14. Department of Surgery, Osaka Prefectural General Medical Center, Osaka, Japan;15. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan;16. Division of Gastroenterology, National Hospital Organization, Shikoku Cancer Center, Matsuyama, Japan;17. Department of Medical Oncology, Kagawa University Hospital, Kagawa, Japan;18. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan;19. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan;20. Frontier Science for Cancer and Chemotherapy, Osaka University, Osaka, Japan;21. Department of Medical Oncology, Kinki University, Osaka, Japan;22. Translational Research Support Section, Clinical Research Support Department, National Cancer Center Hospital East, Kashiwa, Japan;23. Translational Research Support Section, Clinical Research Support Department, National Cancer Center Hospital East, Kashiwa, Japan Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan;24. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan |
| Abstract: | FMS‐like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co‐altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co‐alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non‐FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted. |
| Keywords: | colorectal cancer, copy number status, FLT3 amplification, next‐ generation sequencing, prognosis |