Driver mutations of young lung adenocarcinoma patients with malignant pleural effusion

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.