Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome
Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome
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DOI：
10.1016/j.bbrc.2009.04.004
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发表时间：
2009-05-29
影响因子：
3.1
通讯作者：
Inaba, Toshiya
中科院分区：
文献类型：
--
作者：
Asou, Hiroya;Matsui, Hirotaka;Inaba, Toshiya
7号单体和7号染色体长臂间质缺失(-7/7q-)是一种常见的非随机染色体异常，常见于包括急性髓系白血病(AML)、骨髓增生异常综合征(MDS)和幼年粒单核细胞白血病(JMML)在内的类风湿疾病。利用基于短探针的微阵列比较基因组杂交(MCGH)技术，我们在7q21.3亚带中发现了一个常见的微缺失簇，该簇与常规方法所确定的“热缺失区”相邻。这个常见的微缺失簇包含三个特征不佳的基因：Samd9、Samd9L和一个可能的基因LOC253012，我们将其命名为Miki。实时定量聚合酶链式反应检测3个基因的拷贝数发现，除JMML患者外，AML和MDS成人患者中这3个基因的杂合性缺失频率较高。Miki定位于有丝分裂的纺锤体和中心体，并通过RNA干扰下调Miki，导致有丝分裂和核形态异常，类似于骨髓发育不良。此外，最近的一份报告表明Samd9是一种肿瘤抑制因子。这些发现表明，基于短探针的CGH在检测微缺失方面是有用的。位于7q21.3的3个基因可能是位于7q的髓系肿瘤抑制基因的候选基因。(C)2009 Elsevier Inc.保留所有权利。
Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common non-random chromosomal abnormality found frequently in rnyeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion Cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q. (C) 2009 Elsevier Inc. All rights reserved.