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The t(1;19) chromosomal translocation in acute lymphoblastic pre‐B cell leukemias involves the gene E2A for helix‐loop‐helix (HLH) proteins E12 and E47, ubiquitous transcriptional proteins implicated in the regulation of various lymphoid and nonlymphoid genes. To characterize the molecular features of the t(1;19)(q23;p13) translocation, we molecularly cloned breakpoint DNA from t(1;19)‐carrying pre‐B cell leukemias. In all cases, breakpoints on chromosome 19 occurred within 2 kb of each other in a single intron of the E2A gene. This clustered arrangement resulted in specific truncation of the E2A gene and transcript, with loss of sequences encoding the basic DNA‐binding and HLH dimerization motifs from the derivative 19 chromosome. In contrast, breakpoints on chromosome 1 were distributed over a large region and could not be linked to exonic sequences of the PBX1 gene, although identical chromosome 1 sequences are joined to E2A sequences in 1;19 fusion transcripts. These data show that the 1;19 translocation consistently results in exchange of 3′ exons encoding the HLH motifs of E2A with DNA from chromosome 1 to form a fusion gene on the derivative 19 chromosome.
Genes, Chromosomes and Cancer – Wiley
Published: Sep 1, 1990
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