Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors
Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors
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DOI：
10.1038/modpathol.2008.20
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发表时间：
2008-05-01
期刊：
影响因子：
7.5
通讯作者：
Dhir, Rajiv
中科院分区：
文献类型：
--
作者：
Monzon, Federico A.;Hagenkord, Jill M.;Dhir, Rajiv
复杂或不寻常形态的肾肿瘤需要广泛的检查才能准确分类。染色体畸变定义的亚型肾上皮肿瘤已报告。我们探讨了全基因组染色体拷贝数和单核苷酸多态性（SNP）阵列杂合性丢失分析是否可用于识别这些畸变和分类肾上皮肿瘤。我们分析了20个石蜡包埋的组织，代表透明细胞，乳头状肾和嫌色肾细胞癌，以及嗜酸细胞瘤与Affyssin基因芯片10 K 2.0映射阵列。SNP阵列结果与每个肾肿瘤亚型的已知遗传畸变一致。在所有肾细胞肿瘤类型中均检测到其他染色体畸变。这种独特的模式使20个肿瘤中的19个很容易通过染色体拷贝数畸变进行分类。1例乳头状肾细胞癌2型未显示特征性7/17三体。当使用一组有限的染色体时，使用每个染色体臂的中值拷贝数的聚类与组织学类别相关。此外，分析了三种形态学上具有挑战性的肿瘤，以探索这种方法的潜在临床实用性。在这些情况下，基于SNP阵列的拷贝数评估产生了具有潜在临床价值的信息。这些结果表明，SNP阵列可以检测石蜡包埋的肾肿瘤中的特征性染色体畸变，从而提供了一种高分辨率的全基因组方法，可以用作分类的辅助研究，并可能用于这些肿瘤的预后分层。
Renal tumors with complex or unusual morphology require extensive workup for accurate classification. Chromosomal aberrations that define subtypes of renal epithelial neoplasms have been reported. We explored if whole-genome chromosome copy number and loss-of-heterozygosity analysis with single nucleotide polymorphism (SNP) arrays can be used to identify these aberrations and classify renal epithelial tumors. We analyzed 20 paraffin-embedded tissues representing clear cell, papillary renal and chromophobe renal cell carcinoma, as well as oncocytoma with Affymetrix GeneChip 10K 2.0 Mapping arrays. SNP array results were in concordance with known genetic aberrations for each renal tumor subtype. Additional chromosomal aberrations were detected in all renal cell tumor types. The unique patterns allowed 19 out of 20 tumors to be readily categorized by their chromosomal copy number aberrations. One papillary renal cell carcinoma type 2 did not show the characteristic 7/17 trisomies. Clustering using the median copy number of each chromosomal arm correlated with histological class when using a restricted set of chromosomes. In addition, three morphologically challenging tumors were analyzed to explore the potential clinical utility of this method. In these cases, the SNP array-based copy number evaluation yielded information with potential clinical value. These results show that SNP arrays can detect characteristic chromosomal aberrations in paraffin-embedded renal tumors, and thus offer a high-resolution, genome-wide method that can be used as an ancillary study for classification and potentially for prognostic stratification of these tumors.