The array-based comparative genomic hybridization using microarrayed bacterial artificial chromosome clones allows high-resolution analysis of genome-wide copy number changes in
tumors. To analyze the genetic alterations of primary
lung adenocarcinoma in a high-throughput way, we used
laser-capture microdissection of
cancer cells and array comparative genomic hybridization focusing on 800 chromosomal loci containing
cancer-related genes. We identified a large number of chromosomal numerical alterations, including frequent amplifications on 7p12, 11q13, 12q14-15, and 17q21, and two homozygous deletions on 9p21 and one on 8p23. Unsupervised hierarchical clustering analysis of multiple alterations revealed three subgroups of
lung adenocarcinoma that were characterized by the accumulation of distinct genetic alterations and associated with smoking history and gender. The mutation status of the
epidermal growth factor receptor (EGFR) gene was significantly associated with specific genetic alterations and supervised clustering analysis based on EGFR gene mutations elucidated a subgroup including all EGFR gene mutated
tumors, which showed significantly shorter disease-free survival. Our results suggest that there exist multiple molecular
carcinogenesis pathways in
lung adenocarcinoma that may associate with smoking habits and gender, and that genetic
cancer profiling will reveal previously uncharacterized genetic heterogeneity of
cancer and be beneficial in estimating patient prognosis and discovering novel
cancer-related genes including therapeutic targets.