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年轻肺腺癌伴恶性胸腔积液患者的驱动基因突变。

Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion.

机构信息

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Genes Chromosomes Cancer. 2018 Oct;57(10):513-521. doi: 10.1002/gcc.22647. Epub 2018 Aug 14.

Abstract

Young lung cancer patients have several distinct characteristics. However, there are limited epidemiological data of genetic abnormalities in this population. We conducted a prospective cohort study to delineate the various oncogenic driver mutations of lung adenocarcinoma in young Asian patients. We consecutively collected malignant pleural effusions (MPEs) from lung adenocarcinoma patients. RNA was extracted from MPEs for mutation analysis by reverse transcription-polymerase chain reaction and direct sequencing. Selected gene mutations for testing included EGFR, HER2, BRAF, KRAS, PIK3CA, JAK2, MEK1, NRAS, and AKT2 mutations, as well as EML4-ALK, ROS1, and RET fusions. We collected MPEs from 142 patients aged ≤50 years and 730 patients aged >50 years. Patients aged ≤50 years (91%) had a higher incidence of driver gene mutations than those aged >50 years (84%; P = .036), especially EML4-ALK (P < .001) and ROS1 (P < .001). Among patients aged ≤50 years, EGFR mutation was the major oncogenic driver mutation. The mutation rates of other genes were 18% EML4-ALK, 6% ROS1, 5% HER2, 1% RET, 1% BRAF, and 1% KRAS. We did not detect PIK3CA, JAK2, MEK1, NRAS, or AKT2 mutations. No difference in gender or smoking history was noted among those with different driver mutations. Patients who had a good performance status or received appropriate targeted therapy had longer overall survival. In conclusion, lung adenocarcinoma in Asian patients aged ≤50 years had a higher gene mutation rate than in those aged >50 years, especially EML4-ALK and ROS1 fusion. Mutation analysis may be helpful in determining targeted therapy for the majority of these patients.

摘要

年轻的肺癌患者有几个明显的特征。然而,该人群的遗传异常的流行病学数据有限。我们进行了一项前瞻性队列研究,以描绘亚洲年轻肺癌患者肺腺癌的各种致癌驱动基因突变。我们连续收集了肺腺癌患者的恶性胸腔积液(MPE)。从 MPE 中提取 RNA,通过逆转录-聚合酶链反应和直接测序进行突变分析。用于检测的选定基因突变包括 EGFR、HER2、BRAF、KRAS、PIK3CA、JAK2、MEK1、NRAS 和 AKT2 突变,以及 EML4-ALK、ROS1 和 RET 融合。我们收集了 142 名年龄≤50 岁和 730 名年龄>50 岁的患者的 MPE。年龄≤50 岁的患者(91%)的驱动基因突变发生率高于年龄>50 岁的患者(84%;P=0.036),尤其是 EML4-ALK(P<0.001)和 ROS1(P<0.001)。在年龄≤50 岁的患者中,EGFR 突变是主要的致癌驱动突变。其他基因的突变率为 18%的 EML4-ALK、6%的 ROS1、5%的 HER2、1%的 RET、1%的 BRAF 和 1%的 KRAS。我们没有检测到 PIK3CA、JAK2、MEK1、NRAS 或 AKT2 突变。不同驱动基因突变的患者在性别或吸烟史方面没有差异。表现状态良好或接受适当靶向治疗的患者总生存期更长。总之,亚洲≤50 岁的肺腺癌患者的基因突变率高于>50 岁的患者,尤其是 EML4-ALK 和 ROS1 融合。突变分析可能有助于确定大多数患者的靶向治疗方案。

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