This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schimanski, C. C. Articles by Berger, M. R. Search for Related Content PubMed PubMed Citation Articles by Schimanski, C. C. Articles by Berger, M. R.

Sensitive Detection of K-ras Mutations Augments Diagnosis of Colorectal Cancer Metastases in the Liver

Unit of Toxicology and Chemotherapy, German Cancer Research Center, 69120 Heidelberg, Germany [C. C. S., M. R. B.], and Department of Surgery, Municipal Hospital of Nürnberg, 90419 Nürnberg, Germany [U. L.]

Postoperative survival of colorectal cancer patients is often delineated by metastases spreading to the liver. Current clinical diagnostic procedures are unable to discover micrometastases in this organ. Our aim was to develop a diagnostic tool for detecting micrometastases that are present at the time of surgery. Therefore, a PCR-RFLP assay was set up tracking point mutations of the K-ras oncogene at codons 12 and 13, based on mismatch primers and restriction enzymes BstXI and XcmI. The detection limit of this assay was one mutant in one million wild-type cells. One hundred forty-two patients with colorectal carcinoma were screened for these mutations in tissue samples from their tumor, proximally adjacent mucosa, and liver. Of these, 67 patients (46%) were positive for a K-ras mutation, of which 58 had codon 12 and 9 had codon 13 mutations. No patient without a K-ras-positive tumor showed a mutation in mucosa, but 11 patients with a K-ras-positive tumor (11 of 58; 19%) were found to bear a K-ras mutation in their mucosa, and in 21 patients (21 of 64; 33%), a K-ras mutation was detected in liver tissue. Sequencing of all mutated samples revealed a 92% confirmation of PCR-RFLP results. In summary, the assay is a useful tool for detecting K-ras codon 12 and 13 mutations and allows early proof of molecular determinants of liver metastases. Such knowledge will improve the staging of colorectal cancer patients and could beneficially influence their prognosis if followed by an effective therapy.

This article has been cited by other articles:

				M.-C. Etienne-Grimaldi, J.-L. Formento, M. Francoual, E. Francois, P. Formento, N. Renee, P. Laurent-Puig, M. Chazal, D. Benchimol, J.-R. Delpero, et al. K-Ras Mutations and Treatment Outcome in Colorectal Cancer Patients Receiving Exclusive Fluoropyrimidine Therapy Clin. Cancer Res., August 1, 2008; 14(15): 4830 - 4835. [Abstract] [Full Text] [PDF]

				S. Shahrzad, L. Quayle, C. Stone, C. Plumb, S. Shirasawa, J. W. Rak, and B. L. Coomber Ischemia-Induced K-ras Mutations in Human Colorectal Cancer Cells: Role of Microenvironmental Regulation of MSH2 Expression Cancer Res., September 15, 2005; 65(18): 8134 - 8141. [Abstract] [Full Text] [PDF]

				J. L. Yu, L. May, V. Lhotak, S. Shahrzad, S. Shirasawa, J. I. Weitz, B. L. Coomber, N. Mackman, and J. W. Rak Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis Blood, February 15, 2005; 105(4): 1734 - 1741. [Abstract] [Full Text] [PDF]

				C. P. Dieterle, M. Conzelmann, U. Linnemann, and M. R. Berger Detection of Isolated Tumor Cells by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism for K-ras Mutations in Tissue Samples of 199 Colorectal Cancer Patients Clin. Cancer Res., January 15, 2004; 10(2): 641 - 650. [Abstract] [Full Text] [PDF]

				A. V. Lichtenstein, O.'g. I. Serdjuk, T. I. Sukhova, H. S. Melkonyan, and S. R. Umansky Selective 'stencil'-aided pre-PCR cleavage of wild-type sequences as a novel approach to detection of mutant K-RAS Nucleic Acids Res., September 1, 2001; 29(17): e90 - e90. [Abstract] [Full Text] [PDF]

				E. Lopez-Crapez, T. Livache, J. Marchand, and J. Grenier K-ras Mutation Detection by Hybridization to a Polypyrrole DNA Chip Clin. Chem., February 1, 2001; 47(2): 186 - 194. [Abstract] [Full Text] [PDF]