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[Cancer Research 65, 9152-9154, October 15, 2005]
© 2005 American Association for Cancer Research

Priority Reports

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

Jude Fitzgibbon, Lan-Lan Smith, Manoj Raghavan, Matthew L. Smith, Silvana Debernardi, Spyros Skoulakis, Debra Lillington, T. Andrew Lister and Bryan D. Young

Cancer Research UK Medical Oncology Laboratory, Barts and the Royal London School of Medicine, Queen Mary College, London, United Kingdom

Requests for reprints: Bryan D. Young, Cancer Research UK Medical Oncology Laboratory, Barts and the Royal London School, Charterhouse Square, United Kingdom. Phone: 44-207-882-6002; Fax: 44-207-882-6002; E-mail: bryan.young{at}cancer.org.uk.

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.




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