RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non–Small-Cell Lung Cancer

Author:

Wang Rui1,Hu Haichuan1,Pan Yunjian1,Li Yuan1,Ye Ting1,Li Chenguang1,Luo Xiaoyang1,Wang Lei1,Li Hang1,Zhang Yang1,Li Fei1,Lu Yongming1,Lu Qiong1,Xu Jie1,Garfield David1,Shen Lei1,Ji Hongbin1,Pao William1,Sun Yihua1,Chen Haiquan1

Affiliation:

1. Rui Wang, Haichuan Hu, Yunjian Pan, Yuan Li, Ting Ye, Chenguang Li, Xiaoyang Luo, Lei Wang, Hang Li, Yang Zhang, Yongming Lu, Qiong Lu, Jie Xu, Lei Shen, Yihua Sun, and Haiquan Chen, Fudan University Shanghai Cancer Center; Rui Wang, Haichuan Hu, Yunjian Pan, Yuan Li, Ting Ye, Chenguang Li, Xiaoyang Luo, Lei Wang, Hang Li, Yang Zhang, Yongming Lu, Qiong Lu, Jie Xu, Lei Shen, Yihua Sun, and Haiquan Chen, Shanghai Medical College, Fudan University; David Garfield, ProMed Cancer Centers; Fei Li and Hongbin...

Abstract

Purpose The RET fusion gene has been recently described in a subset of non–small-cell lung cancers (NSCLCs). Because we have limited knowledge about these tumors, this study was aimed at determining the clinicopathologic characteristics of patients with NSCLC harboring the RET fusion gene. Patients and Methods We examined the RET fusion gene in 936 patients with surgically resected NSCLC using a reverse transcriptase polymerase chain reaction (PCR) plus quantitative real-time PCR strategy, with validation using immunohistochemical and fluorescent in situ hybridization assays. A subset of 633 lung adenocarcinomas was also studied for EGFR, KRAS, HER2, and BRAF mutations, as well as ALK rearrangements. Patient characteristics, including age, sex, smoking history, stage, grade, International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of subtypes of lung adenocarcinoma, and relapse-free survival, were collected. Results Of 936 patients with NSCLC, the RET fusion gene was exclusively detected in 13 patients (11 of 633 patients with adenocarcinomas and two of 24 patients with adenosquamous cell carcinomas). Of the 13 patients, nine patients had KIF5B-RET, three patients had CCDC6-RET, and one patient had a novel NCOA4-RET fusion. Patients with lung adenocarcinomas with RET fusion gene had more poorly differentiated tumors (63.6%; P = .029 for RET v ALK, P = .007 for RET v EGFR), with a tendency to be younger (≤ 60 years; 72.7%) and never-smokers (81.8%) and to have solid subtype (63.6%) and a smaller tumor (≤ 3 cm) with N2 disease (54.4%). The median relapse-free survival was 20.9 months. Conclusion RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung adenocarcinomas and has identifiable clinicopathologic characteristics, warranting further clinical consideration and targeted therapy investigation.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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