Alvarez Karla, Kash Shera F, Lyons-Weiler Maureen A, Kim Hyun-Jung, Peterson Leif E, Mathai Benita, Hagenkord Jill M, Monzon Federico A
Department of Pathology, The Methodist Hospital and The Methodist Hospital Research Institute, Houston, TX, USA.
Diagn Mol Pathol. 2010 Sep;19(3):127-34. doi: 10.1097/PDM.0b013e3181d527c5.
Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalances may assist in the diagnosis, prognosis, and/or therapeutic management of certain neoplasms. Several methods for detecting chromosomal imbalances, such as, fluorescent in situ hybridization, array comparative genomic hybridization, and single nucleotide polymorphism (SNP) arrays have proven useful in formalin-fixed paraffin-embedded (FFPE) tissues. Here, we report the performance and reproducibility of virtual karyotyping of FFPE tissues with Affymetrix SNP arrays.
Virtual karyotypes from 442 FFPE tumor samples were generated using the Affymetrix GeneChip Mapping 10K Xba 2.0 and/or 250K Nsp SNP mapping arrays. Samples ranged from a few weeks to 17 years in archival storage. Virtual karyotypes were assessed for copy number changes, loss of heterozygosity, and acquired uniparental disomy.
Overall, 75.3% of samples produced interpretable virtual karyotypes with the 10K arrays and 76.7% in the 250K arrays. Parameters for the selection of samples for hybridization were determined, which increased the success rate in both platforms to 81.3 and 92.6%, respectively. FFPE virtual karyotypes generated with both 10K Xba 2.0 and 250K Nsp arrays showed 100% concordance in intralaboratory and interlaboratory reproducibility studies. Samples older than 7 years showed decreased performance.
SNP arrays are a reliable, reproducible, and robust platform for the virtual karyotyping of FFPE tumor tissues with performance characteristics adequate for clinical application. Parameters that most significantly affected sample performance were sample age and storage conditions.
染色体失衡在癌症和遗传性疾病中很常见。这些失衡可能有助于某些肿瘤的诊断、预后和/或治疗管理。几种检测染色体失衡的方法，如荧光原位杂交、阵列比较基因组杂交和单核苷酸多态性（SNP）阵列，已被证明在福尔马林固定石蜡包埋（FFPE）组织中很有用。在此，我们报告使用Affymetrix SNP阵列对FFPE组织进行虚拟核型分析的性能和可重复性。
使用Affymetrix GeneChip Mapping 10K Xba 2.0和/或250K Nsp SNP映射阵列生成442个FFPE肿瘤样本的虚拟核型。样本的存档时间从几周至17年不等。对虚拟核型进行拷贝数变化、杂合性缺失和获得性单亲二体性评估。
总体而言, 10K阵列对75.3%的样本产生了可解释的虚拟核型，250K阵列的这一比例为76.7%。确定了杂交样本选择参数，这分别将两个平台的成功率提高到81.3%和92.6%。使用10K Xba 2.0和250K Nsp阵列生成FFPE虚拟核型在实验室内和实验室间重复性研究中显示出100%的一致性。超过7年的样本性能下降
SNP阵列是用于FFPE肿瘤组织虚拟核型分析的可靠、可重复且强大的平台，其性能特征足以用于临床应用。对样本性能影响最显著的参数是样本年龄和保存条件。
