Cytogenetic Studies: (1) A new type of MPC-associated translocation was identified. The IgH carrying chromosome 12 segment underwent a paracentric inversion. The inverted segment was translocated onto chromosome 15. The breakpoint on chromosome 15 is band D where the c-myc was mapped. (2) The orientation of c-myc and IgH was determined by sorting the MPC-associated t(12;15) translocation chromosome and hybridizing its DNA with relevant probes. The orientation c-myc is centromere 5' - 3'-telomere and that of IgH is centromere-C?H?-V?H?-telomere. (3) In situ hybridization on inv. Rb(6;15) chromosome has established that the chromosome 6 segment that carries the kappa gene is translocated onto chromosome 15 in the MPC-associated variant translocation and is juxtaposed to c-myc in a tail to head fashion. (4) The order of genes on the t(15;6) chromosome is centromere-5'-c-myc-3' pvt-1-C?K?-telomere. (5) The orientation Ig-kappa on chromosome 6 was also established: centromere V?K?-C?K?-telomere. Molecular Studies: (1) The molecular analysis of the ABPC 45 deletion MPC revealed that the c-myc gene has been involved in multiple translocation/recombination events which placed the oncogene under the control of the IgH chain gene enhancer. (2) In the rat, the c-myc gene has been assigned to chromosome 7. We have mapped the immunoglobulin heavy and kappa light chain genes to chromosomes 6 and 4, respectively. Chromosomes 6 and 7 take part in the reciprocal chromosomal translocation characteristic to the spontaneous rat immunocytomas. We have demonstrated that the chromosomal breakpoints on the chromosome 7 fall outside the coding region of the c-myc oncogene. (3) We have found that the insertion of the proviral DNA into the vicinity of c-myc and other chromosome 15 (c-sis, int-1, Mlvi-1, Mlvi-2) or chromosome 17 (pim-1) associated oncogenes is an infrequent event in the MCF and MoMuLV virus induced murine T-cell lymphoma/leukemia and is independent of 15-trisomy. (4) We have demonstrated that in human plasma cell leukemia the c-myc oncogene is amplified 25 to 30 fold, with a 20-fold increase in transcriptional activity. (M)
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