Analysis of the joining sequences of the t(15;17) translocation in human acute promyelocytic leukemia: Sequence non-specific recombination between the pml and rara genes within identical short stretches
✍ Scribed by Hitoshi Yoshida; Tomoki Naoe; Hisashi Fukutani; Hitoshi Kiyoi; Kazuaki Kubo; Ryuzo Ohno
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 885 KB
- Volume
- 12
- Category
- Article
- ISSN
- 1045-2257
No coin nor oath required. For personal study only.
✦ Synopsis
Molecular analysis of the t ( 15; 17) translocation in 70 patients with acute promyelocytic leukemia (APL) confirmed that the breakpoints of chromosome I5 were located in two regions of the promyelocytic leukemia (PML) gene, mainly introns 3 and 6, whereas the breakpoints of chromosome I 7 were consistently in intron 2 of the retinoic acid receptor alpha (RAM) gene.
To study the reason for the clustering of the breakpoints and the underlying mechanism of the chromosomal translocation, we characterized the joining sequences of der( 15) and der( 17) by polymerase chain reaction in samples from eight patients with APL. There was no cluster of the breakpoints within the introns, and no consensus sequence-motif was found around them. One or nine extra nucleotides were inserted into two joining sites. There were identical stretches of one t o seven nucleotides between the PML and RARA genes in the majority of the joining sequences. These data provide a potential model of the t ( I 5; 17) translocation: random D N A double strand cleavage, modification of D N A ends by enzymes including terminal deoxynucleotidyl transferase, and single strand base-pairing within identical short stretches. Furthermore, APL develops only when the PML and RAM genes are rearranged within restricted genomic regions and a functional PML-RARA chimeric product is produced, and this might lead t o a clustering of the breakpoints. Genes Chromosorn Cancer 1237-44 (1995).