Chromosomal imbalances in lung adenocarcinomas with or without mutations in the epidermal growth factor receptor gene.
OBJECTIVE
Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinomas of Asian patients, implying a good response to treatment with the EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. However, the distinct chromosomal imbalances between lung adenocarcinomas with and those without EGFR mutations have not been fully elucidated.


METHODS
Seventy-seven patients of surgically resected lung adenocarcinoma were analysed for the EGFR exon 19 deletion and the L858R mutation, using mutant-enriched PCR, and for chromosomal imbalance alterations using comparative genomic hybridization.


RESULTS
EGFR mutations were detected in 42 (54.5%) patients, including 22 with the exon 19 deletion and 20 with the L858R mutation. The mean number of chromosomal arms with imbalance alterations was significantly higher in tumours with EGFR mutations than in those lacking these two mutations. The minimal regions with gain on 1q23-q31, 6p12-p21.1 and 7q11.2, and loss on 3p21, 8p22-p23, 9q33, 10q25 and 13q13, differed significantly between lung adenocarcinomas with or without EGFR mutations. However, neither EGFR mutations, nor any of the common chromosomal imbalance alterations alone, exhibited significant associations with tumour stage or disease-specific survival of the patients.


CONCLUSIONS
These results indicate that imbalance alterations at several chromosomal regions occur significantly more frequently in lung adenocarcinomas with EGFR mutations than in those without such mutations. Tumour growth-related genes in these chromosomal regions should be further investigated to improve our understanding of the common genetic alterations in lung adenocarcinomas with EGFR mutations.
Fong
Yao
Y
Division of Thoracic Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
Lin
Yue-Shan
YS
Liou
Chiou-Ping
CP
Li
Chien-Fen
CF
Tzeng
Ching-Cherng
CC
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002869:Chromosome Aberrations; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
D066246:ErbB Receptors