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

Hyunki Kim, Woo Nam Suk, Hwanseok Rhee, Shan Li Long, Ju Kang Hyun, Hye Koh Kwi, Kyu Kim Nam, Jaehwi Song, Edison Tak Bun Liu, Hoguen Kim

Research output: Contribution to journalArticle

43 Scopus citations

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 17334 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.

Original languageEnglish (US)
Pages (from-to)6218-6225
Number of pages8
JournalOncogene
Volume23
Issue number37
DOIs
StatePublished - Aug 19 2004

Keywords

  • Colorectal carcinomas
  • Gene expression profile
  • Microsatellite instability
  • Molecular classification
  • Oligonucleotide microarray

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Kim, H., Suk, W. N., Rhee, H., Long, S. L., Hyun, J. K., Kwi, H. K., Nam, K. K., Song, J., Liu, E. T. B., & Kim, H. (2004). Different gene expression profiles between microsatellite instability-high and microsatellite stable colorectal carcinomas. Oncogene, 23(37), 6218-6225. https://doi.org/10.1038/sj.onc.1207853