Association between acquired uniparental disomy and homozygous gene mutation in acute myeloid leukemias
Association between acquired uniparental disomy and homozygous gene mutation in acute myeloid leukemias
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DOI：
10.1158/0008-5472.can-05-2017
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发表时间：
2005-10-15
期刊：
影响因子：
11.2
通讯作者：
Young, BD
中科院分区：
文献类型：
--
作者：
Fitzgibbon, J;Smith, LL;Young, BD
全基因组单核苷酸多态性分析显示，在类似于20%的急性髓性白血病中，大规模的隐性区域获得性纯合性以节段性单亲二体性的形式存在。我们已经研究了这些区域，这是有丝分裂重组的结果，是否包含已知的突变靶基因在白血病的纯合突变。在13例单亲二体性病例中的7例中，我们在4个不同的基因座（WT1、FLT3、CEBPA和RUNX1）发现了并发的纯合突变。这意味着突变先于有丝分裂重组，其作为负责去除剩余野生型等位基因的“第二次打击”，如最近在骨髓增生性疾病中的JAK2基因所示。
Genome-wide single nucleotide polymorphism analysis has revealed large-scale cryptic regions of acquired homozygosity in the form of segmental uniparental disomy in similar to 20% of acute myeloid leukemias. We have investigated whether such regions, which are the consequence of mitotic recombination, contain homozygous mutations in genes known to be mutational targets in leukemia. In 7 of 13 cases with uniparental disomy, we identified concurrent homozygous mutations at four distinct loci (WT1, FLT3, CEBPA, and RUNX1). This implies that mutation precedes mitotic recombination which acts as a "second hit" responsible for removal of the remaining wildtype allele, as has recently been shown for the JAK2 gene in myeloproliferative disorders.