Novel regions of acquired uniparental disomy discovered in acute myeloid leukemia

被引:67
作者
Gupta, Manu [1 ]
Raghavan, Manoj [1 ]
Gale, Rosemary E. [2 ]
Chelala, Claude [3 ,4 ]
Allen, Christopher [2 ]
Molloy, Gael [1 ]
Chaplin, Tracy [1 ]
Linch, David C. [2 ]
Cazier, Jean-Baptiste [1 ,5 ]
Young, Bryan D. [1 ]
机构
[1] Barts & London, Sch Med, Med Oncol Ctr, Genom Unit, London EC1M 6BQ, England
[2] UCL Royal Free & Univ Coll Med Sch, Dept Haematol, London WC1E 6HX, England
[3] Barts & London, Sch Med, Ctr Mol Oncol, Inst Canc, London EC1M 6BQ, England
[4] Barts & London, Sch Med, Canc Res UKCIin Ctr, London EC1M 6BQ, England
[5] Canc Res UK Bioinformat & Biostat Serv, London WC2A 3PX, England
关键词
D O I
10.1002/gcc.20573
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 non-random 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 aUPD 13q (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 aUPD 13q covering the FLT3 gene. Significantly, none of the samples with FLT3-ITD-/FLT3-TKD+ mutation exhibited aUPD 13q. 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. (C) 2008 Wiley-Liss, Inc.
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收藏
页码:729 / 739
页数:11
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