Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies
Implementation of high resolution single nucleotide polymorphism array analysis as a clinical test for patients with hematologic malignancies
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DOI：
10.1016/j.cancergencyto.2010.10.007
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发表时间：
2011-01-01
期刊：
影响因子：
1.9
通讯作者：
Biegel, Jaclyn A.
中科院分区：
文献类型：
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作者：
Dougherty, Margaret J.;Wilmoth, Donna M.;Biegel, Jaclyn A.
基于单核苷酸多态性的寡核苷酸阵列已被用作检测多种血液恶性肿瘤和实体肿瘤基因组拷贝数变化和等位基因失衡的研究工具。高分辨率、全基因组覆盖、最小的DNA需求和相对较短的周转时间有利于在临床环境中使用。我们通过分析127例儿童白血病和淋巴瘤样本，验证了Illumina HumanHap550 Bead芯片阵列的临床应用，这些样本之前已经通过标准细胞遗传学分析和荧光原位杂交进行了表征。更高分辨率的Illumina HumanHap610头芯片阵列最终用于临床测试。迄今为止，已分析了180份疑似或确诊血液恶性肿瘤儿童的样本。在180例临床样本中，有130例（72%）骨髓或淋巴瘤样本存在核型中未见的阵列畸变。这些典型的缺失包括与B细胞或t细胞恶性肿瘤相关的基因缺失，如CDKN2A/B、PAX5和IKZF1。在该队列的49个样本中，还检测到75个拷贝数中性杂合性缺失区域（bbb5mb阈值），可归类为体质或获得性异常。根据我们过去2年的经验，我们认为单核苷酸多态性阵列是血液学恶性肿瘤标准细胞遗传学方法的一个有价值的补充，但不是替代。
Single nucleotide polymorphism based oligonucleotide arrays have been used as a research tool to detect genomic copy number changes and allelic imbalance in a variety of hematologic malignancies and solid tumors. The high resolution, genome-wide coverage, minimal DNA requirements, and relatively short turnaround time are advantageous for use in a clinical setting. We validated the Illumina HumanHap550 Bead Chip array for clinical use by analyzing 127 pediatric leukemia and lymphoma samples that had previously been characterized by means of standard cytogenetic analysis and fluorescence in situ hybridization. A higher resolution Illumina HumanHap610 Bead Chip array was ultimately used for clinical testing. To date, 180 samples from children with a suspected or confirmed hematologic malignancy have been analyzed. Of the 180 clinical samples, 130 (72%) bone marrow or lymphoma specimens had aberrations revealed by the array that were not seen in the karyotypes. These typically included deletions in genes associated with B- or T-cell malignancies, such as CDKN2A/B, PAX5, and IKZF1. There were also 75 regions of copy number neutral loss of heterozygosity (>5 Mb threshold) detected in 49 samples in this cohort, which could be categorized as constitutional or acquired abnormalities. On the basis of our experience in the last 2 years, we suggest that single nucleotide polymorphism arrays are a valuable addition to, but not a replacement for, standard cytogenetic approaches for hematologic malignancies.