FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

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

doi:10.1111/cas.14693

FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

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 NishidaHisato Kawakami, Yasutoshi Sakamoto, Izumi Miki, Wataru Okamoto, Kentaro Yamazaki, Takayuki Yoshino

Gastrointestinal Surgery (2)

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	314-322
Number of pages	9
Journal	Cancer Science
Volume	112
Issue number	1
DOIs	https://doi.org/10.1111/cas.14693
Publication status	Published - Jan 2021

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cas.14693

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Hasegawa, H., Taniguchi, H., Nakamura, Y., Kato, T., Fujii, S., Ebi, H., Shiozawa, M., Yuki, S., Masuishi, T., Kato, K., Izawa, N., Moriwaki, T., Oki, E., Kagawa, Y., Denda, T., Nishina, T., Tsuji, A., Hara, H., Esaki, T., ... Yoshino, T. (2021). FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer. Cancer Science, 112(1), 314-322. https://doi.org/10.1111/cas.14693

Hasegawa, H, Taniguchi, H, Nakamura, Y, Kato, T, Fujii, S, Ebi, H, Shiozawa, M, Yuki, S, Masuishi, T, Kato, K, Izawa, N, Moriwaki, T, Oki, E, Kagawa, Y, Denda, T, Nishina, T, Tsuji, A, Hara, H, Esaki, T, Nishida, T, Kawakami, H, Sakamoto, Y, Miki, I, Okamoto, W, Yamazaki, K & Yoshino, T 2021, 'FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer', Cancer Science, vol. 112, no. 1, pp. 314-322. https://doi.org/10.1111/cas.14693

@article{03dfade850bf455eae9ea50900572486,

title = "FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer",

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.",

author = "Hiroko Hasegawa and Hiroya Taniguchi and Yoshiaki Nakamura and Takeshi Kato and Satoshi Fujii and Hiromichi Ebi and Manabu Shiozawa and Satoshi Yuki and Toshiki Masuishi and Ken Kato and Naoki Izawa and Toshikazu Moriwaki and Eiji Oki and Yoshinori Kagawa and Tadamichi Denda and Tomohiro Nishina and Akihito Tsuji and Hiroki Hara and Taito Esaki and Tomohiro Nishida and Hisato Kawakami and Yasutoshi Sakamoto and Izumi Miki and Wataru Okamoto and Kentaro Yamazaki and Takayuki Yoshino",

note = "Funding Information: This work was supported by SCRUM‐Japan funds. We appreciate the participation of patients and contribution of the members that participated in this study. We would like to thank Editage for English language review. Funding Information: This work was supported by SCRUM-Japan funds. We appreciate the participation of patients and contribution of the members that participated in this study. We would like to thank Editage for English language review. Publisher Copyright: {\textcopyright} 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2021",

month = jan,

doi = "10.1111/cas.14693",

language = "English",

volume = "112",

pages = "314--322",

journal = "Cancer Science",

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T1 - FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

AU - Hasegawa, Hiroko

AU - Taniguchi, Hiroya

AU - Nakamura, Yoshiaki

AU - Kato, Takeshi

AU - Fujii, Satoshi

AU - Ebi, Hiromichi

AU - Shiozawa, Manabu

AU - Yuki, Satoshi

AU - Masuishi, Toshiki

AU - Kato, Ken

AU - Izawa, Naoki

AU - Moriwaki, Toshikazu

AU - Oki, Eiji

AU - Kagawa, Yoshinori

AU - Denda, Tadamichi

AU - Nishina, Tomohiro

AU - Tsuji, Akihito

AU - Hara, Hiroki

AU - Esaki, Taito

AU - Nishida, Tomohiro

AU - Kawakami, Hisato

AU - Sakamoto, Yasutoshi

AU - Miki, Izumi

AU - Okamoto, Wataru

AU - Yamazaki, Kentaro

AU - Yoshino, Takayuki

N1 - Funding Information: This work was supported by SCRUM‐Japan funds. We appreciate the participation of patients and contribution of the members that participated in this study. We would like to thank Editage for English language review. Funding Information: This work was supported by SCRUM-Japan funds. We appreciate the participation of patients and contribution of the members that participated in this study. We would like to thank Editage for English language review. Publisher Copyright: © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

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JO - Cancer Science

JF - Cancer Science

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ER -

FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

Abstract

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