Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of
EGFR as well as the aberrant promoter methylations of
BRCA1,
MGMT,
MLH1, and
RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic
EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with
EGFR or
BRCA1 methylation but not
EGFR mutation. In addition,
EGFR,
BRCA1,
MGMT,
MLH1, and
RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The
RASSF1A methylation was found to be linked to the smoking habit. Methylations in
MGMT and
RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of
EGFR mutation and that of
BRCA1,
MGMT or
RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of
EGFR mutations through blocking expression due to promoter
EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.
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