A CHROMOSOME 12 CODING REGION IS JUXTAPOSED TO THE MYC PROTOONCOGENE LOCUS IN A T(8,12)(Q24,Q22) TRANSLOCATION IN A CASE OF B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

We performed molecular cloning and sequencing of the breakpoints of a new chromosomal translocation involving the MYC protooncogene locus. This secondary t(8;12)(q24;q22) was associated with a primary t(11;14)(q13;q32) translocation in a case of B-cell chronic lymphocytic leukemia (CLL) in blastic transformation. In this leukemia, Northern blot and nuclease analyses SI showed that MYC was strongly expressed with initiation of the transcription at both the 5' and 3' promoters as observed in Burkitt's lymphomas; no coding change was observed in MYC putative regulatory sequences. The breakpoint on chromosome 8 mapped to the 3' end of the MYC locus, in a region containing a potential Z-DNA tract, and where we identified two DNase 1 hypersensitive sites. A rearranged MYC gene fragment was cloned and shown to contain chromosome 12 information by Southern blot analysis and by in situ hybridization. A genomic probe subcloned from the isolated region of the chromosome 12 recognized a 1.8 kb transcript in virtually all the tissues tested but a preferential expression of this new gene, which we termed BTG1 (for B-cell translocation gene 1) was observed in the CLL cells and in tissues of lymphoid origin. This chromosome 12 coding sequence is conserved in evolution and a transcript of similar size is present in murine tissues.