日本国家癌症中心Koichi Goto、Susumu S. Kobayashi等研究人员合作发现,CLIP1-LTK融合是非小细胞肺癌的致癌驱动因素。相关论文于2021年11月24日在线发表在《自然》杂志上。
Title: The CLIP1–LTK fusion is an oncogenic driver in non‐small‐cell lung cancer
Author: Izumi, Hiroki, Matsumoto, Shingo, Liu, Jie, Tanaka, Kosuke, Mori, Shunta, Hayashi, Kumiko, Kumagai, Shogo, Shibata, Yuji, Hayashida, Takuma, Watanabe, Kana, Fukuhara, Tatsuro, Ikeda, Takaya, Yoh, Kiyotaka, Kato, Terufumi, Nishino, Kazumi, Nakamura, Atsushi, Nakachi, Ichiro, Kuyama, Shoichi, Furuya, Naoki, Sakakibara-Konishi, Jun, Okamoto, Isamu, Taima, Kageaki, Ebi, Noriyuki, Daga, Haruko, Yamasaki, Akira, Kodani, Masahiro, Udagawa, Hibiki, Kirita, Keisuke, Zenke, Yoshitaka, Nosaki, Kaname, Sugiyama, Eri, Sakai, Tetsuya, Nakai, Tokiko, Ishii, Genichiro, Niho, Seiji, Ohtsu, Atsushi, Kobayashi, Susumu S., Goto, Koichi
Issue&Volume: 2021-11-24
Abstract: Lung cancer is one of the most aggressive tumour types. Targeted therapies stratified by oncogenic drivers have substantially improved therapeutic outcomes in patients with non-small-cell lung cancer (NSCLC)1. However, such oncogenic drivers are not found in 25–40% of cases of lung adenocarcinoma, the most common histological subtype of NSCLC2. Here we identify a novel fusion transcript of CLIP1 and LTK using whole-transcriptome sequencing in a multi-institutional genome screening platform (LC-SCRUM-Asia, UMIN000036871). The CLIP1–LTK fusion was present in 0.4% of NSCLCs and was mutually exclusive with other known oncogenic drivers. We show that kinase activity of the CLIP1–LTK fusion protein is constitutively activated and has transformation potential. Treatment of Ba/F3 cells expressing CLIP1–LTK with lorlatinib, an ALK inhibitor, inhibited CLIP1–LTK kinase activity, suppressed proliferation and induced apoptosis. One patient with NSCLC harbouring the CLIP1–LTK fusion showed a good clinical response to lorlatinib treatment. To our knowledge, this is the first description of LTK alterations with oncogenic activity in cancers. These results identify the CLIP1–LTK fusion as a target in NSCLC that could be treated with lorlatinib.
DOI: 10.1038/s41586-021-04135-5
Source: https://www.nature.com/articles/s41586-021-04135-5
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
本期文章:《自然》:Online/在线发表