Comparative Genomic Hybridization of Human Lung Cancer

Lung cancer is a highly aggressive neoplasm, a characteristic that is reflected by the multitude of genetic aberrations detectable on the chromosomal and molecular level. In order to understand these seemingly chaotic chromosomal alterations, we have performed Comparative Genomic Hybridization (CGH) on a large collective of human lung carcinomas. CGH was one of the first screening methods used to analyze tumor genomes for genetic imbalances (1 ,2 ), and has rapidly become a popular tool for a comprehensive molecular cytogenetic analysis of solid tumors. The method is based on the hybridization of differentially labeled tumor and reference DNA on normal chromosome metaphase spreads. Both genomes compete for complementary binding sites on the chromosomal DNA. In the case of an amplification in tumor DNA, more DNA will hybridize to the corresponding band or chromosomal arm, whereas deletions will allow the binding of the normal DNA to competitively prevail. Detection of each genome is facilitated by the use of distinct fluorochrome labels. DNA imbalances are determined by comparing the intensity of the fluorescence signals along individual chromosomes. DNA gains are potentially associated with the activation of proto-oncogenes and DNA losses with the inactivation of tumor-suppressor genes.