Gupta Manu, Raghavan Manoj, Gale Rosemary E, Chelala Claude, Allen Christopher, Molloy Gael, Chaplin Tracy, Linch David C, Cazier Jean-Baptiste, Young Bryan D
Cancer Genomics Unit, Medical Oncology Centre, Barts and the London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
Genes Chromosomes Cancer. 2008 Sep;47(9):729-39. doi: 10.1002/gcc.20573.
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.
急性髓系白血病（AML）中单亲二体（aUPD）的获得导致已知基因突变纯合。发现aUPD的新区域有可能识别先前未知的突变靶点。因此，我们旨在绘制AML中aUPD区域图谱。在此，我们使用基因分型阵列分析了大量来自年轻成年人（年龄：15 - 55岁）的诊断性AML样本（n = 454）。在17%的样本中发现了获得性UPD，其分布非随机，尤其影响染色体臂13q、11p和11q。在2p、17p、2q、17q、1p和Xq发现了aUPD的新的复发区域。总体而言，在所有细胞遗传学风险组中均观察到aUPD，尽管具有aUPD13q的样本（占样本的5.4%）仅属于细胞遗传学定义的中危组。所有先前测量的FLT3 - ITD水平高的病例均有覆盖FLT3基因的aUPD13q。值得注意的是，具有FLT3 - ITD（ - ）/FLT3 - TKD（ + ）突变的样本均未表现出aUPD13q。在观察到的119个aUPD中，大多数（87%）是由于有丝分裂重组，而只有13%是由于不分离。本研究表明aUPD在AML中是一个常见且重要的发现，并确定了可能包含新突变靶点的区域。
