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(American Journal of Pathology. 2003;163:1985-1995.)
© 2003 American Society for Investigative Pathology

Accurate Molecular Classification of Human Cancers Based on Gene Expression Using a Simple Classifier with a Pathological Tree-Based Framework

Kerby A. Shedden^*, Jeremy M. G. Taylor, Thomas J. Giordano, Rork Kuick, David E. Misek, Gad Rennert^¶, Donald R. Schwartz^||, Stephen B. Gruber^||, Craig Logsdon^**, Diane Simeone, Sharon L. R. Kardia, Joel K. Greenson, Kathleen R. Cho^||, David G. Beer, Eric R. Fearon^|| and Samir Hanash

From the Departments of Statistics,^*Biostatistics,Pathology,Pediatrics,Internal Medicine,^||Physiology,^**Surgery,and Epidemiology,and the Comprehensive Cancer Center, the University of Michigan, Ann Arbor, Michigan; and the National Cancer Control Center,^¶Clalit Health Service and Technion University, Haifa University, Haifa, Israel

Recent studies suggest accurate prediction of tissue of origin for human cancers can be achieved by applying sophisticated statistical learning procedures to gene expression data obtained from DNA microarrays. We have pursued the hypothesis that a more straightforward and equally accurate strategy for classifying human tumors is to use a simple algorithm that considers gene expression levels within a tree-based framework that encodes limited information about pathology and tissue ontogeny. By considering gene expression data within this framework, we found only a small number of genes were required to achieve a relatively high accuracy level in tumor classification. Using as few as 45 genes we were able to classify 157 of 190 human malignant tumors correctly, which is comparable to previous results obtained with sophisticated classifiers using thousands of genes. Our simple classifier accurately predicted the origin of metastatic tumors even when the classifier was trained using only primary tumors, and the classifier produced accurate predictions when trained and tested on expression data from different labs, and from different microarray platforms. Our findings suggest that accurate and robust cancer diagnosis from gene expression profiles can be achieved by mimicking the classification strategies routinely used by surgical pathologists.

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