The Molecular Revolution in Cutaneous Biology: Era of Cytogenetics and Copy Number Analysis

Development of karyotyping techniques in the 1950s sparked groundbreaking reports of chromosomal aberrations in cancer, such as the Philadelphia chromosome in chronic myelogenous leukemia in 1960, followed by a number of others. Spatial resolution of karyotyping is limited and vital tumor cells are required for metaphase preparation. To overcome these limitations, DNA hybridization techniques were developed. In situ hybridization of radioactively or fluorescence labeled RNA probes onto tumor samples allowed the identification of specific genomic regions, translocations and copy number alterations. However, it is only suited for a limited number of candidate genes or regions. Genome-wide copy number analysis was made possible by the development of comparative genomic hybridization. It compares an entire cancer genome to a normal genome by differential fluorescence labeling and hybridization onto normal metaphase chromosomes. Replacing the metaphase chromosomes with arrays of oligonucleotides significantly increased the resolution. Karyotypic analysis of melanomas could demonstrate chromosomal aberrations decades ago. However, only CGH allowed understanding the complex melanoma genomes. Based on mutation analysis and CGH data, Boris Bastian and his group changed our view of melanoma towards a variety of genetically distinct tumors. Recent next generation sequencing allows simultaneous mutation, translocation and copy number analysis, and thereby accelerates melanoma research.