The long term priority of this aspect of the Laboratory of Cancer Genetics is the development and implementation of methods integrating molecular and cytogenetic technologies in the study of cancer. The impetus for this effort is largely derived from the inadequacy of older technologies to deal with the complex changes in the structure of the genome and the myriad alterations of gene expression which occur during oncogenesis. Improvements in technology for placing molecular probes onto the cytogenetic map combined with the ability to convert cytogenetically observable structures into discrete molecular reagents now provide an important pathway for information flow between the molecular and cytogenetic arenas. Chromosome microdissection has provided a key technology for generating the reagents which facilitate this effort. 1) High-resolution positional reagents and visualization methods encompass microdissection technology as well as high-resolution fluorescence and multicolor in situ hybridization (FISH). These methods are being applied to the analysis of previously intractable problems in cancer cytogenetics. A new technology, the use of cDNA microarrays, has been developed to allow simultaneous evaluation of cellular mRNA levels for thousands of genes. This technology specifically enables sensitive comparisons of gene transcript levels between cells from various pathological stages. (Experiments to date with a model system in which tumorigenic potential is genetically suppressed demonstrate that the method allows detection of many changes in gene expression associated with an important biological event.) This system which, for the first time, enables the global analysis of gene expression in cancer cells, is being applied to both clinical specimens and laboratory models of cancer development and progression.
