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Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas

Abstract

Most colon cancers are thought to develop through the ‘adenoma-to-carcinoma sequence’ model. To elucidate the mechanisms underlying this pathway, we analysed gene-expression profiles of 20 colorectal tumors (nine adenomas and 11 differentiated adenocarcinomas) by means of a cDNA microarray representing 23 040 genes coupled with laser-capture microdissection. A two-dimensional hierarchical clustering analysis of expression profiles of the 20 tumors correctly separated the carcinoma group from the adenoma group. Furthermore we identified 51 genes whose expression was commonly up-regulated, 376 that were commonly down-regulated in both types of tumors as opposed to normal colonic epithelium and 50 whose expression levels were significantly different between adenomas and carcinomas. On the basis of expression profiles of the 50 discriminating genes, we established a scoring system to separate adenomas from carcinomas. Application of this scoring system for evaluating five additional colorectal tumors correctly predicted their histological features. The genome-wide information reported here should contribute to a more profound understanding of colorectal tumorigenesis, particularly of adenoma-carcinoma progression, and provide indicators for developing novel strategies to diagnose, treat, and ultimately prevent colorectal carcinomas.

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Acknowledgements

We appreciate the help of Drs Yoshinao Yamada, Yoshiyuki Akiyama, Masataka Sakaguchi, Osamu Kitahara, and Renpei Yanagawa for helpful discussions, and the assistance of Dr Meiko Takahashi in preparing the manuscript. This work was supported in part by Research for the Future Program Grant #00L01402 from the Japan Society for the Promotion of Science.

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Correspondence to Yusuke Nakamura.

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Lin, YM., Furukawa, Y., Tsunoda, T. et al. Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas. Oncogene 21, 4120–4128 (2002). https://doi.org/10.1038/sj.onc.1205518

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