Modern strategy of tumor suppressor gene cloning: B-cell chronic lymphocytic leukemia candidate genes search as an illustration.

Genes that normally function to prevent or suppress malignancy are known as "tumor suppressor genes" or TSG. It is supposed that the chromosomal regio n lost in the tumor cells harbors TSG preventing cancer. The examination of this region in the normal chromosome would permit identification of the pa rticular suppressor gene. The methods employed in such search are diverse. As a rule, success is achieved by combining cytogenetic, genetic and physic al genome mapping with analysis of genomic and cDNA clones. We have constru cted a cosmid contig in the 13q14.3 region which is expected to contain a p utative B-cell chronic lymphocytic leukemia (BCLL) TSG, cDNA clones corresp onding to new human gene Leu5 have been found to locate nearby the borders of homo- and hemizygous deletions in BCLL patients. Gene Leu5 encodes a zin c-finger protein that shares homology with some mammalian genes taking part in early embryogenesis and tumor progression. Leu5 gene could be an intere sting candicate for BCLL TSG.