Application of targeted next-generation sequencing in non-small cell lung cancer
10.3969/j.issn.1000-8179.2018.11.083
- VernacularTitle:靶向高通量测序在非小细胞肺癌中的临床应用
- Author:
Yanan CHENG
1
;
Yingnan YE
;
Li DONG
;
Lei HAN
;
Pengpeng LIU
;
Rui ZHANG
;
Jinpu YU
Author Information
1. 天津医科大学肿瘤医院肿瘤分子诊断中心国家肿瘤临床医学研究中心天津市肿瘤防治重点实验室天津市恶性肿瘤临床医学研究中心
- Keywords:
next-generation sequencing;
non-small cell lung cancer (NSCLC);
driver gene;
individualized diagnosis and treatment
- From:
Chinese Journal of Clinical Oncology
2018;45(11):582-588
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To detect eight highly related driver genes in non-small cell lung cancer (NSCLC), and to analyze the relationship between gene variations and clinical-pathological features. Methods: We collected 212 NSCLC samples from Tianjin Medical University Cancer Institute and Hospital, and sequenced eight genes which are EGFR, KRAS, BRAF, ALK, MET, ERBB2, ROS1 and RET. Results: EGFR gene variation rate was as high as 52.8%, followed by KRAS (8.5%), ALK (8.0%), ERBB2 (6.1%), MET (3.8%), BRAF (1.4%), RET (0.9%) and ROS1 (0.9%) in eight detecting genes, at least one driver gene variant was detected in 75% samples, and driver gene variant showed strong mutual exclusion. The most common EGFR mutations were 19 exon deletion and L858R mutation, and the mutation of EGFR T790M was accompanied by the above two mutations. The proportion of non-EGFR T790M mutations in patients with exon 19 dele-tion was lower than that of L858R mutations (P=0.04). There were 15.2% patients with EGFR mutation accompanied by EGFR amplifica-tion, and the proportion of patients with EGFR mutation frequency greater than 40% with EGFR amplification was higher than that without EGFR amplification (P<0.01). Women, non-smoking, patients with adenocarcinoma were prone to carry EGFR especially EGFR sensitive mutations (P<0.01). Patients with lung adenocarcinoma (P=0.013), late clinical stage (P=0.048), and lymph node metastasis (P=0.027) had a higher proportion of EGFR amplification. The incidence of KRAS mutation was higher in men, left lung cancer and smoking patients (P=0.009, P=0.048, P=0.037). Patients with non-KRAS mutations, ALK fusions were younger (P=0.005, P=0.031), and with KRAS mutations were older (P=0.055). Conclusions: Next-generation sequencing (NGS) can simultaneously detect eight highly re-lated driver genes in NSCLC patients to provide evidence for clinicians. NGS based on detection of multiple genes provides more possi- bilities for individualized diagnosis and treatment of NSCLC.
