Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases

Abstract

Purpose: To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations.

Patients and methods: In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1.

Results: Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations.

Conclusion: To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Oncogenic driver mutations in East Asian never-smokers with lung adenocarcinomas. In tumors from 52 patients, 78.8% (41 of 52) harbored EGFR kinase domain mutations, 5.8% (three of 52) harbored EML4-ALK fusions, 3.8% (two of 52) harbored HER2 mutations, and 1.9% (one of 52) harbored KRAS mutations. Only 9.6% (five of 52) of tumors did not harbor any of these known oncogenic driver mutations.