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- Title
Molecular Classification of Human Cancers Using a 92-Gene Real-Time Quantitative Polymerase Chain Reaction Assay.
- Authors
Xiao-Jun Ma; Patel, Rajesh; Xianqun Wang; Salunga, Ranelle; Murage, Jaji; Desai, Rupal; Tuggle, J. Todd; Wei Wang; Chu, Shirley; Stecker, Kimberly; Raja, Rajiv; Robin, Howard; Moore, Mat; Baunoch, David; Sgroi, Dennis; Erlander, Mark
- Abstract
Context.—Correct diagnosis of the tissue origin of a metastatic cancer is the first step in disease management, but it is frequently difficult using standard pathologic methods. Microarray-based gene expression profiling has shown great promise as a new tool to address this challenge. Objective.—Adoption of microarray technologies in the clinic remains limited. We aimed to bridge this technological gap by developing a real-time quantitative polymerase chain reaction (RT-PCR) assay. Design.—We constructed a microarray database of 466 frozen and 112 formalin-fixed, paraffin-embedded (FFPE) samples of both primary and metastatic tumors, measuring expression of 22 000 genes. From the microarray database, we used a genetic algorithm to search for gene combinations optimal for multitumor classifi- cation. A 92-gene RT-PCR assay was then designed and used to generate a database for 481 frozen and 119 FFPE tumor samples. Results.—The microarray-based K-nearest neighbor classifier demonstrated 84% accuracy in classifying 39 tumor types via cross-validation and 82% accuracy in predicting 112 independent FFPE samples. We successfully translated the microarray database to the RT-PCR platform, which allowed an overall success rate of 87% in classifying 32 different tumor classes in the validation set of 119 FFPE tumor samples. Conclusions.—The RT-PCR-based expression assay involving 92 genes represents a powerful tool for accurately and objectively identifying the site of origin for metastatic tumors, especially in the cases of cancer of unknown primary. The assay uses RT-PCR and routine FFPE samples, making it suitable for rapid clinical adoption.
- Subjects
TUMORS; GENES; ALGORITHMS; ONCOLOGY; MICROBIOLOGICAL assay; GENE expression
- Publication
Archives of Pathology & Laboratory Medicine, 2006, Vol 130, Issue 4, p465
- ISSN
0003-9985
- Publication type
Article
- DOI
10.5858/2006-130-465-mcohcu