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

Sun Y, Ren Y, Fang Z, Li C, Fang R, Gao B, Han X, Tian W, Pao W, Chen H, Ji H
J Clin Oncol. 2010 28 (30): 4616-20

PMID: 20855837 · PMCID: PMC2974342 · DOI:10.1200/JCO.2010.29.6038

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.

MeSH Terms (25)

Adenocarcinoma Adult Aged Asian Continental Ancestry Group Chi-Square Distribution China Class I Phosphatidylinositol 3-Kinases DNA Mutational Analysis ErbB Receptors Female Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Humans Lung Neoplasms Male Middle Aged Mutation Oncogene Proteins, Fusion Oncogenes Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins p21(ras) ras Proteins Receptor, ErbB-2 Tumor Suppressor Protein p53

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