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Genome-Wide Single Nucleotide Polymorphism Analysis Reveals Frequent Partial Uniparental Disomy Due to Somatic Recombination in Acute Myeloid Leukemias

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

Requests for reprints: Bryan D. Young, Cancer Research UK Medical Oncology Laboratory, Barts and the Royal London School of Medicine and Dentistry, Queen Mary College, Charterhouse Square, London EC1 6BQ, United Kingdom. Phone: 44-207-882-6002; Fax: 44-207-882-6004; E-mail: bryan.young{at}cancer.org.uk.

Genome-wide analysis of single nucleotide polymorphisms in 64 acute myeloid leukemias has revealed that 20% exhibited large regions of homozygosity that could not be accounted for by visible chromosomal abnormalities in the karyotype. Further analysis confirmed that these patterns were due to partial uniparental disomy (UPD). Remission bone marrow was available from five patients showing UPD in their leukemias, and in all cases the homozygosity was found to be restricted to the leukemic clone. Two examples of UPD11p were shown to be of different parental origin as indicated by the methylation pattern of the H19 gene. Furthermore, a previously identified homozygous mutation in the CEBPA gene coincided with a large-scale UPD on chromosome 19. These cryptic chromosomal abnormalities, which seem to be nonrandom, have the characteristics of somatic recombination events and may define an important new subclass of leukemia.

Key Words: single nucleotide polymorphisms • microarray • acute myeloid leukemia • karyotype • genotype

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