Acquirement of DNA copy number variations in non-small cell lung cancer metastasis to the brain.

Brain metastasis is a major complication of non-small cell lung cancer (NSCLC) and leads to most of the mortality of this disease. However, the biological mechanisms and molecular features in brain metastasis of NSCLC are poorly understood. In the present study, we compared whole-genome copy number variations (CNVs) between a primary lung adenocarcinoma and secondary metastatic brain lesion from the same patient using array comparative genomic hybridization (aCGH). The number of CNV regions was markedly higher in the secondary metastatic tumor than the primary tumor in the lung. In detail, the common CNVs in both tumors included gains of 7p22, 7p12-p11, 7q11, 7q22, 21q22, and 19q13; gains of 1p33-p34, 1q22, 5p13 and 14q11 whereas losses of 3p, 4q31, 5q, 11p15, Xp21-p22 and Xq21 were identified only in the secondary lesion. Gene Ontology enrichment analysis revealed that the genes with amplified copy numbers in both tumors were related to such processes as DNA replication and mismatch repair. Genes only amplified in the metastatic tumor were enriched in processes that include leukocyte migration and organ development, and genes with a lower copy number in the secondary tumor included the processes of proteolysis regulation, negative regulation of cell proliferation and cell adhesion. These findings provided new insight into the genomic mechanism of the spread of lung adenocarcinoma to the brain, and the candidate genes identified serve as novel indicators or putative targets in NSCLC brain metastasis.