We noted that the t(14:18)(q32:q21) chromosomal translocation characteristic of follicular B cell lymphomas had a focused breakpoint at the 5' end of immunoglobulin (Ig) joining (JH) segments and had extronucleotide """"""""N"""""""" segments inserted at the chromosomal juncture. This indicates that Ig recombinase mediates the breakage on chromosome 14. However analysis of the breakpoint on chromosomal 18 reveals that a random staggered dsDNA break interrupts an exon of a B cell associated gene. This gene is normally highly expressed in pre B cells but down-regulated with differentiation, but translocation results in an elevated amount of a fusion transcript with the Ig locus. We've isolated cDNAs of the normal as well as translocated gene. We identified small major breakpoint region where over 70% of these translocation cluster and have used this marker of a transformation event to follow the clonal evolution of neoplasms and to refine cytogenetics of lymphomas. We have further characterized the Kappa deleting element (Kde) which eliminates Kappa genes prior to Gamma light chain Ig use. We've found aberrantly rearranged V/J recombinants up stream of 75% of Kde rearrangements and noted that 75% of the time the Kde may rearrange directly with the VK segment. We've noted duplication of the Kde and have chromosomally mapped related genes. We extensively characterized the T Cell Receptor (TCR) and Ig gene in T as well as pre B form of acute lymphoblastic leukemia (ALL). Unique subsets of T cells were identified that were genetically indeterminant, or had unanticipated patterns of TCR Alpha, Beta, Gamma gene rearrangement and expression. Moreover, a striking lineage spillover of Gamma TCR gene rearrangement was noted in pre B cell ALLs in contrast to mature B cells indicating they are a distinct subset of early B cell precursors.
