Tissue microarrays for high-throughput molecular profiling of tumor specimens
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Updated: Apr 1, 2026
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
J Kononen1, L Bubendorf, A Kallioniemi
1Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4470, USA.
Abstract:
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. 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.
Insights
Researchers developed a high-throughput microarray technique to analyze gene expression and copy number in thousands of tumors. This method aids in identifying new cancer genes and defining tumor subgroups for better diagnostics and therapeutics.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Cancer development involves complex genetic and signaling pathways.
- Existing gene expression analysis tools are limited in analyzing large patient cohorts.
- Identifying novel cancer genes requires analyzing numerous tumor specimens.
Purpose of the Study:
- To develop a high-throughput technique for comprehensive gene expression and copy number analysis across a large number of tumors.
- To enable parallel in situ detection of DNA, RNA, and protein targets within individual tumor biopsies.
- To facilitate the rapid analysis of hundreds of molecular markers in the same set of specimens.
Main Methods:
- Development of an array-based high-throughput technique.
- Construction of tumor tissue microarrays containing up to 1000 tissue biopsies per array.
- Parallel in situ detection of DNA, RNA, and protein targets using consecutive microarray sections.
Main Results:
- Successful detection of six gene amplifications in breast cancer specimens.
- Analysis of p53 and estrogen receptor expression in breast cancer.
- Demonstration of the technique's power in defining new tumor subgroups.
Conclusions:
- The developed microarray technique enables efficient molecular profiling of large tumor cohorts.
- This approach accelerates the identification and validation of novel cancer genes.
- The technique facilitates the discovery of new tumor subgroups with potential diagnostic and therapeutic implications.
