Our group develops and applies molecular cytogenetic techniques to identify chromosomal aberrations in human carcinogenesis and in animal models thereof. These techniques comprise fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and spectral karyotyping (SKY). CGH and SKY are cytogenetic screening tests that allow one to survey tumor genomes for numerical and structural chromosomal aberrations. CGH is based on quantitative fluorescence in situ hybridization and produces a karyogram of chromosomal imbalances in tumor genomes. SKY allows the visualization of all human (and other species) chromosomes in different colors based on the measurement of discrete and chromosomes specific emission spectra by means of spectral imaging.

The application of these techniques to the genesis of colorectal tumors and tumors of the uterine cervix has identified a pattern of chromosomal aberrations that is tumor-specific and tumor stage-specific. The emergence of specific chromosomal aberrations coincides with impaired p53 function, which is a consequence of mutation inactivation or the presence of high risk human papilloma viruses.

Animal models are valuable tools to dissect the specific function of tumor suppressor genes or oncogenes on the maintenance of chromosomal stability. The analysis of tumors of the mammary gland in c-myc transgenic mice revealed a recurrent pattern of chromosomal aberrations. SKY of lymphomas that originate in mice deficient for the ataxia telangiectasia gene suggest a common translocation event and will become useful to understand the role of these aberrations in human disease.

Further research in our group will be directed towards the elucidation of cell biological aspects of chromosomal aberrations in premalignant diseases and cancer.