Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia.
The acquisition of uniparental disomy (aUPD) in acute myeloid leukemia (AML) results in homozygosity for known gene mutations. Uncovering novel regions of aUPD has the potential to identify previously unknown mutational targets. We therefore aimed to develop a map of the regions of aUPD in AML. Here, we have analyzed a large set of diagnostic AML samples (n = 454) from young adults (age: 15-55 years) using genotype arrays. Acquired UPD was found in 17% of the samples with a nonrandom distribution particularly affecting chromosome arms 13q, 11p, and 11q. Novel recurrent regions of aUPD were uncovered at 2p, 17p, 2q, 17q, 1p, and Xq. Overall, aUPDs were observed across all cytogenetic risk groups, although samples with aUPD13q (5.4% of samples) belonged exclusively to the intermediate-risk group as defined by cytogenetics. All cases with a high FLT3-ITD level, measured previously, had aUPD13q covering the FLT3 gene. Significantly, none of the samples with FLT3-ITD(-)/FLT3-TKD(+) mutation exhibited aUPD13q. Of the 119 aUPDs observed, the majority (87%) were due to mitotic recombination while only 13% were due to nondisjunction. This study demonstrates aUPD is a frequent and significant finding in AML and pinpoints regions that may contain novel mutational targets.
Cancer Genomics Unit, Medical Oncology Centre, Barts and the London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
Manu
M
Gupta
Manoj
M
Raghavan
Rosemary E
RE
Gale
Claude
C
Chelala
Christopher
C
Allen
Gael
G
Molloy
Tracy
T
Chaplin
David C
DC
Linch
Jean-Baptiste
JB
Cazier
Bryan D
BD
Young
D000328:Adult; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D024182:Uniparental Disomy / Q000235:genetics*