TISSUE MICROARRAYS FOR HIGH-THROUGHPUT MOLECULAR PROFILING OF TUMOR SPECIMENS

Many genes and signalling pathways controlling cell proliferation, dea th and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene ex pression and cDNA microarrays, have enabled measurement of the express ion 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 h undreds of specimens from patients in different stages of disease is n eeded to establish the diagnostic, prognostic and therapeutic importan ce of each of the emerging cancer gene candidates. Here we have develo ped an array-based high-throughput technique that facilitates gene exp ression and copy number surveys of very large numbers of tumors. As ma ny as 1000 cylindrical tissue biopsies from individual tumors can be d istributed in a single tumor tissue microarray, Sections of the microa rray provide targets for parallel in situ detection of DNA, RNA and pr otein 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.