Nature Medicine
4, 844 - 847 (1998)
doi:10.1038/nm0798-844
Tissue microarrays for high-throughput molecular profiling of tumor specimensJuha Kononen1, Lukas Bubendorf2, Anne Kallionimeni1, Maarit Bärlund3, Peter Schraml2, Stephen Leighton4, Joachim Torhorst2, Michael J Mihatsch2, Guido Sauter2
& Olli-P. Kallionimeni1, 5
1Laboratory of Cancer Genetics, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4470, Room 4A24, Bethesda, MD 20892-4470, USA
2Institute of Pathology, University of Basel, Switzerland
3Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere, Finland
4Beecher Instruments, Silver Spring, MD, USA
5Correspondence should be addressed to O−P.K; email: okalli@nhgri.nih.gov 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 genes1,2. 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.
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