Tissue microarrays for high-throughput molecular profiling of tumor specimens
Tissue microarrays for high-throughput molecular profiling of tumor specimens
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DOI：
10.1038/nm0798-844
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发表时间：
1998-07-01
期刊：
影响因子：
82.9
通讯作者：
Kallioniemi, OP
中科院分区：
文献类型：
--
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
许多控制细胞增殖、死亡和分化以及基因组完整性的基因和信号通路参与癌症的发展。新的技术，如基因表达和cDNA微阵列的系列分析，已经能够在一个实验中测量数千个基因的表达，揭示了许多新的，潜在的重要癌症基因（1，2）。这些基因组筛查工具可以一次全面调查一种肿瘤;然而，需要分析来自不同疾病阶段患者的数百份标本，以确定每种新兴癌症候选基因的诊断，预后和治疗重要性。在这里，我们开发了一种基于阵列的高通量技术，有助于基因表达和大量肿瘤的拷贝数调查。来自个体肿瘤的多达1000个圆柱形组织活检可以分布在单个肿瘤组织微阵列中，微阵列的切片提供用于阵列上的每个标本中的DNA、RNA和蛋白质靶的平行原位检测的靶，并且连续切片允许快速分析同一组标本中的数百个分子标记。我们对乳腺癌中6个基因扩增以及p53和雌激素受体表达的检测证明了这种技术用于定义新的肿瘤亚组的能力。
Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes(1,2). These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray, Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.