Association between Acquired Uniparental Disomy and Homozygous Gene Mutation in Acute Myeloid Leukemias
- 15 October 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 65 (20), 9152-9154
- https://doi.org/10.1158/0008-5472.can-05-2017
Abstract
Genome-wide single nucleotide polymorphism analysis has revealed large-scale cryptic regions of acquired homozygosity in the form of segmental uniparental disomy in ∼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.Keywords
This publication has 18 references indexed in Scilit:
- Genomewide Single Nucleotide Polymorphism Microarray Mapping in Basal Cell Carcinomas Unveils Uniparental Disomy as a Key Somatic EventCancer Research, 2005
- A Gain-of-Function Mutation ofJAK2in Myeloproliferative DisordersNew England Journal of Medicine, 2005
- Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosisCancer Cell, 2005
- A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia veraNature, 2005
- Development of a human acute myeloid leukaemia screening panel and consequent identification of novel gene mutation in FLT3 and CCND3British Journal of Haematology, 2005
- Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2Genes, Chromosomes and Cancer, 2003
- Identification of RUNX1/AML1 as a classical tumor suppressor geneOncogene, 2003
- Loss of Heterozygosity Associated with Uniparental Disomy in Breast CarcinomaLaboratory Investigation, 2002
- Mutations of theWT1 gene in childhood nonlymphoid hematological malignanciesGenes, Chromosomes and Cancer, 1999
- Loss of Heterozygosity or: How I Learned to Stop Worrying and Love Mitotic RecombinationAmerican Journal of Human Genetics, 1997