HIGH-LEVEL DNA AMPLIFICATIONS ARE COMMON GENETIC ABERRATIONS IN B-CELL NEOPLASMS

Gene amplification is one of the molecular mechanisms resulting in the up-regulation of gene expression. In non-Hodgkin's lymphomas, such ge ne amplifications have been identified rarely, Using comparative genom ic hybridization, a technique that has proven to be very sensitive for the detection of high-level DNA amplifications, are analyzed 108 case s of B-cell neoplasms (42 chronic B-cell leukemias, 5 mantle cell lymp homas, and 61 aggressive B-cell lymphomas). Twenty-four high-level amp lifications were identified in 13% of the patients and mapped to 15 di fferent genomic regions, Regions most frequently amplified were bands XQ26-28, 2p23-24, and 2p14-16 as well as 18q21 (three times each), Amp lification of several proto-oncogenes and a cell cycle control gene (N -MYC (two cases), BCL2, CCND2, and GLI) located within the amplified r egions was demonstrated by Southern blot analysis or fluorescence in s itu hybridization to interphase nuclei of tumor cells, These data demo nstrate that gene amplifications in B-cell neoplasms are much more fre quent than previously assumed. The identification of highly amplified DNA regions and genes included in the amplicons provides important inf ormation for further analyses of genetic events involved in lymphomage nesis.