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K-ras mutations and RASSF1A promoter methylation in colorectal cancer

Oncogene volume 21, pages 3792–3795 (2002)Cite this article

Abstract

Human cancer is characterized by genetic and epigenetic alterations. In this study we provide evidence for the interruption of Ras signaling in sporadic colorectal cancer (CRC) by either genetic activation of the K-ras oncogene or epigenetic silencing of the putative tumor suppressor gene RASSF1A. Paraffin embedded tumor tissue samples from 222 sporadic CRC patients were analysed for K-ras codon 12 and codon 13 activating mutations and RASSF1A promoter hypermethylation. Overall, K-ras mutations were observed in 87 of 222 (39%) and RASSF1A methylation was observed in 45 of 222 (20%) of CRCs. Mutation of K-ras alone was detected in 76 of 222 (34%) CRCs. RASSF1A promoter methylation with wild-type K-ras was observed in 34 of 222 (15%) CRCs. In 101 of 222 (46%) CRCs neither K-ras mutations nor RASSF1A methylation was observed and 11 of 222 (5%) CRCs showed both K-ras mutations and RASSF1A methylation. These data show that the majority of the studied CRCs with K-ras mutations lack RASSF1A promoter methylation, an event which occurs predominantly in K-ras wild-type CRCs (P=0.023, Chi-square test).

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Acknowledgements

We thank Stephen B Baylin for helpful suggestions and for critically reading the manuscript and Michael G House for providing normal colon tissue. This work was supported in part by grants from the Dutch Cancer Society and the Rene Vogels Foundation.

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Authors and Affiliations

  1. Department of Pathology, University Maastricht, P.O. Box 616, Maastricht, 6200, MD, The Netherlands

    Manon van Engeland, Guido MJM Roemen, Marco MM Pachen, Adriaan P de Bruïne, Jan-Willem Arends & Anton FPM de Goeij

  2. Department of Epidemiology, University Maastricht, P.O. Box 616, Maastricht, 6200, MD, The Netherlands

    Mirian Brink, Matty P Weijenberg & Piet A van den Brandt

  3. Tumor Biology, The Johns Hopkins Oncology Center, 1650 Orleans Street, Room 543, Baltimore, 21231, Maryland, MD, USA

    Manon van Engeland & James G Herman

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  1. Manon van Engeland
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Correspondence to James G Herman.

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van Engeland, M., Roemen, G., Brink, M. et al. K-ras mutations and RASSF1A promoter methylation in colorectal cancer. Oncogene 21, 3792–3795 (2002). https://doi.org/10.1038/sj.onc.1205466

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