High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration
High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration
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DOI：
10.1038/sj.leu.2404145
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发表时间：
2006-05-01
期刊：
影响因子：
11.4
通讯作者：
Johansson, B
中科院分区：
文献类型：
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作者：
Paulsson, K;Heidenblad, M;Johansson, B
虽然作为唯一染色体畸变的8三体是急性髓性白血病（AML）和骨髓增生异常综合征（MDS）中最常见的数字异常，但对其致病作用知之甚少。考虑到+8是AML/MDS中常见的继发性改变，8三体作为明显的单一异常，可能会出现隐性的-可能是原发性的-遗传畸变。然而，没有此类隐藏异常的报道。我们对10例分离的+8 AML/MDS病例进行了高分辨率全基因组阵列比较基因组杂交（array CGH）分析，利用32K的细菌人工染色体阵列集，提供498%的基因组覆盖率，分辨率为100 kb。在4/10的病例中，阵列CGH显示染色体内失衡，不对应于已知的基因组拷贝数多态性，包括9个重复和半合子缺失，大小从0.5到2.2 Mb不等。在MDS转化为AML时，在+8之前，在7p14.1处发现了1.8Mb的缺失。此外，在一个病例中存在包括ETV6的缺失。其余7种失衡涉及40多个基因。目前的研究结果表明，在8-三体阳性的AML/MDS病例中，隐性遗传异常是常见的，+8作为唯一的细胞遗传畸变并不总是主要的遗传事件。
Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic - possibly primary - genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing 498% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.