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Different gene expression profiles between microsatellite instability-high and microsatellite stable colorectal carcinomas

Oncogene volume 23, pages 6218–6225 (2004)Cite this article

Abstract

Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability (CIN) and microsatellite instability (MSI), exist in colorectal carcinomas. In order to clarify the molecular signature related to the CIN and MSI in colorectal carcinomas, we performed transcriptomic expression analysis on eight microsatellite instability-high (MSI-H) colorectal carcinomas and compared the results obtained with that of nine microsatellite stable (MSS) colorectal carcinomas using oligonucleotide microarrays containing 17 334 known genes and 1331 unknown genes or expression sequence tags (ESTs). Unsupervised two-way hierarchical clustering with 5724 genes successfully classified tumors from normal mucosa, and displayed a distinctive MSI-H carcinomas subgroup. Based on intensive filtering, 57 known genes and eight ESTs were found to be highly relevant to the differentiation of MSI-H and MSS colorectal carcinomas. These genes successfully distinguish the new test set of six MSI-H and five MSS colorectal carcinomas. Many up- and downregulated genes in MSI-H colorectal carcinomas were related to the previously reported phenotypic characteristics; increased mucin production and intense peritumoral immune response in MSI-H carcinomas. Some of these differences were confirmed by semiquantitative reverse transcription–PCR and immunohistochemical analysis. Our findings indicate that there are many different genetic and transcriptomic characteristics between MSI-H and MSS colorectal carcinomas, and some of these differently expressed genes can be used as diagnostic or prognostic markers.

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Acknowledgements

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (03-PJ10-PG6-GP01-0002) and the Cancer Metastasis Research Center at Yonsei University.

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Author notes

  1. Contributed equally to this study

Authors and Affiliations

  1. Department of Pathology, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Hyunki Kim, Long Shan Li, Hyun Ju Kang, Kwi Hye Koh & Hoguen Kim

  2. Brain Korea 21 Projects for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Hyunki Kim, Hwanseok Rhee, Long Shan Li, Hyun Ju Kang & Kwi Hye Koh

  3. Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Suk Woo Nam, Jaehwi Song & Hoguen Kim

  4. Department of Surgery, Yonsei University College of Medicine, Seoul, 120-752, Korea

    Nam Kyu Kim

  5. Genome Institute of Singapore, 138672, Singapore

    Edison Tak-Bun Liu

  6. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, 137-710, Korea

    Suk Woo Nam

  7. Department of Genetic Engineering, College of Life Science and Natural Resources, Sungkyunkwan University, Suwon, 440-746, Korea

    Jaehwi Song

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  1. Hyunki Kim
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Correspondence to Hoguen Kim.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Kim, H., Nam, S., Rhee, H. et al. Different gene expression profiles between microsatellite instability-high and microsatellite stable colorectal carcinomas. Oncogene 23, 6218–6225 (2004). https://doi.org/10.1038/sj.onc.1207853

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  • DOI: https://doi.org/10.1038/sj.onc.1207853

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