Genomic anatomy of the specific reciprocal translocation t(15;17) in acute promyelocytic leukemia.
Genomic anatomy of the specific reciprocal translocation t(15;17) in acute promyelocytic leukemia.
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急性早幼粒细胞白血病特异性相互易位 t(15;17) 的基因组解剖学。
DOI：
10.1002/gcc.10154
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发表时间：
2003
期刊：
影响因子：
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中科院分区：
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作者：
Reiter,Andreas;Saussele,Susanne;Grimwade,David;Wiemels,JosephL;Segal,MarkR;Lafage-Pochitaloff,Marina;Walz,Christoph;Weisser,Andreas;Hochhaus,Andreas;Willer,Andreas;Reichert,Anja;Büchner,Thomas;Lengfelder,Eva;Hehlmann,Rüdiger;
The genomic breakpoints in the t(15;17)(q22;q21), associated with acute promyelocytic leukemia (APL), are known to occur within three differentPMLbreakpoint cluster regions (bcr) on chromosome 15 and withinRARAintron 2 on chromosome 17; however, the precise mechanism by which this translocation arises is unclear. To clarify this mechanism, we (i) assembled the sequence ofRARAintron 2, (ii) amplified and sequenced the genomicPML‐RARAjunction sequences from 37 APL patients, and (iii) amplified and sequenced the reverseRARA‐PMLgenomic fusion in 29 of these cases. Three significant breakpoint microclusters withinRARAintron 2 were identified, suggesting that sequence‐associated or structural factors play a role in the formation of the t(15;17). There was no evidence that the location of a breakpoint inPMLhad any relationship to the location of the corresponding breakpoint inRARA. Although some sequence motifs previously implicated in illegitimate recombinations were found in the microcluster regions, these associations were not significant. Comparison of forward and reverse genomic junctions revealed microhomologies, deletions, and/or duplications of either gene in all but one case, in which a complex rearrangement with inversion of thePML‐derived sequence was found. These findings are consistent with the hypothesis that the t(15;17) occurs by nonhomologous recombination of DNA after processing of the double‐strand breaks by a dysfunctional DNA damage‐repair mechanism. © 2003 Wiley‐Liss, Inc.
