title: Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias.
abstract: Genome-wide analysis of single nucleotide polymorphisms in 64 acute myeloid leukemias has revealed that approximately 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.
authors.affiliation: Cancer Research UK Medical Oncology Laboratory, Barts and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
authors.forename: Manoj
authors.initials: M
authors.lastname: Raghavan
authors.forename: Debra M
authors.initials: DM
authors.lastname: Lillington
authors.forename: Spyros
authors.initials: S
authors.lastname: Skoulakis
authors.forename: Silvana
authors.initials: S
authors.lastname: Debernardi
authors.forename: Tracy
authors.initials: T
authors.lastname: Chaplin
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Foot
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D005260:Female; D015894:Genome, Human; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy
chemical_list: D004273:DNA, Neoplasm