Kashuba V. Novel tumor suppressor genes of epithelial cancers

The subject - molecular mechanisms of cancergenesis; the aim is the identification, structural and functional characteristics of novel tumour suppressor genes from human chromosome 3, which are associated with renal, lung and other type of cancer; the methods of molecular biology and biochemistry were applied; the novelty lies in the construction of libraries of NotI linking and NotI jumping clones using the modern methods. For the first time, human chromosome 3 was mapped using NotI clones. We have determined the regions on 3p21.3 that are the most often deleted in the different cancers and built their physical and gene map. In these regions more than 50 genes are localized. More than 20 novel genes were identified and their nucleotide and aminoacid sequences of their protein products were determined. The new method to detect suppressor activity of genes-candidates was developed. More than 20 genes were studied by this method, named GIT (gene inactivation test). Such genes, as RASSF1A, RASSF1C (в KRC/Y), RBSP3A, RBSP3B, G21/NPRL2, SEMA3B, HYAL1, HYAL2, FUS1, ТP53, RB1 have suppressed the tumor growth in SCID mice. New markers for diagnostics are identified. It was shown that TSG candidates may be inactivated not only due to mutations or deletions but may be inacivated epigenetically due to their promotor region methylation.