Association between Acquired Uniparental Disomy and Homozygous Gene Mutation in Acute Myeloid Leukemias

作者：Jude Fitzgibbon, Lan‐Lan Smith, Manoj Raghavan, Matthew L. Smith, Silvana Debernardi, Spyros Skoulakis, Debra M. Lillington, Tim A. Lister, Bryan D. Young · 发表于：Cancer Research · 年份：2005 · DOI：10.1158/0008-5472.can-05-2017 · 被引用次数：245 · 研究领域：Myeloproliferative Neoplasms: Diagnosis and Treatment、Acute Myeloid Leukemia Research、Chronic Myeloid Leukemia Treatments

Genome-wide single nucleotide polymorphism analysis has revealed large-scale cryptic regions of acquired homozygosity in the form of segmental uniparental disomy in approximately 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 wild-type allele, as has recently been shown for the JAK2 gene in myeloproliferative disorders.