This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tórtola, S. Articles by Reymond, M. A. Search for Related Content PubMed PubMed Citation Articles by Tórtola, S. Articles by Reymond, M. A. Social Bookmarking                            What's this?

Discordance Between K-ras Mutations in Bone Marrow Micrometastases and the Primary Tumor in Colorectal Cancer

From the Fondation Pour Recherches Médicales, Geneva, Switzerland; Departments of Surgery and Pathology, Carl-Thiem-Klinikum, Cottbus, and Department of Surgery, Otto-von-Guericke University, Magdeburg, Germany; and Institut de Recerca Oncològica, Hospital Duran i Reynals, Barcelona, Spain.

Address reprint requests to Marc A. Reymond, MD, Department of Surgery, Otto-von-Guericke University, Leipziger Str 44, D-39120 Magdeburg, Germany; email: marc.reymond{at}medizin.uni-magdeburg.de

PURPOSE: To study bone marrow micrometastases from colorectal cancer patients for the presence of K-ras mutations and to compare their genotype with that of the corresponding primary tumor.

PATIENTS AND METHODS: Bilateral iliac crest aspiration was performed in 51 patients undergoing surgery for colorectal cancer, and bone marrow micrometastases were detected by immunohistochemistry. The presence of K-ras mutations was determined by single-strand conformation polymorphism analysis on both primary tumors and paired bone marrow samples and was confirmed by sequencing.

RESULTS: In six patients with primary tumor mutations, it was possible to amplify a mutated K-ras gene also from the bone marrow sample. In three of those patients the pattern of K-ras mutations differed between both samples, in two patients the mutation was identical between the bone marrow and its primary tumor, and in one patient the same mutation plus a different one were found. Fifteen of 17 K-ras mutations found in primary tumors were located in codon 12, whereas in bone marrow, five of seven mutations were found in codon 13 (P = .003).

CONCLUSION: Our results demonstrate that, at least for K-ras mutations, disseminated epithelial cells are not always clonal with the primary tumor and they question the malignant genotype of bone marrow micrometastases. They also indicate that different tumoral clones may be circulating simultaneously or sequentially in the same patient. Analysis of the type of mutations suggests that cell dissemination might be an early event in colorectal carcinogenesis.

S.T. and R.S. contributed equally to this study.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C.-H. Gow, Y.-L. Chang, Y.-C. Hsu, M.-F. Tsai, C.-T. Wu, C.-J. Yu, C.-H. Yang, Y.-C. Lee, P.-C. Yang, and J.-Y. Shih Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer Ann. Onc., April 1, 2009; 20(4): 696 - 702. [Abstract] [Full Text] [PDF]

				A. Marchetti, G. Gasparini, M. Albitar, C. Yeh, W. Ma, W. De Roock, D. Lambrechts, S. Tejpar, T. Winder, W. Scheithauer, et al. K-ras Mutations and Cetuximab in Colorectal Cancer N. Engl. J. Med., February 19, 2009; 360(8): 833 - 836. [Full Text] [PDF]

				R. Steinert and M. A. Reymond Demonstration of the Presence of Circulating Tumor Cells as Evidence of Metastatic Potential--Reply Arch Surg, November 1, 2008; 143(11): 1134 - 1134. [Full Text] [PDF]

				S. Artale, A. Sartore-Bianchi, S. M. Veronese, V. Gambi, C. S. Sarnataro, M. Gambacorta, C. Lauricella, and S. Siena Mutations of KRAS and BRAF in Primary and Matched Metastatic Sites of Colorectal Cancer J. Clin. Oncol., September 1, 2008; 26(25): 4217 - 4219. [Full Text] [PDF]

				R. Steinert, M. Hantschick, M. Vieth, I. Gastinger, F. Kuhnel, H. Lippert, and M. A. Reymond Influence of Subclinical Tumor Spreading on Survival After Curative Surgery for Colorectal Cancer Arch Surg, February 1, 2008; 143(2): 122 - 128. [Abstract] [Full Text] [PDF]

				R Steinert, M Vieth, M Hantschick, and M A Reymond Epithelial cells disseminate into the bone marrow of colorectal adenoma patients Gut, July 1, 2005; 54(7): 1045 - 1046. [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]

				M. R. Weihrauch, E. Skibowski, T. C. Koslowsky, W. Voiss, D. Re, F. Kuhn-Regnier, C. Bannwarth, M. Siedek, V. Diehl, and H. Bohlen Immunomagnetic Enrichment and Detection of Micrometastases in Colorectal Cancer: Correlation With Established Clinical Parameters J. Clin. Oncol., November 1, 2002; 20(21): 4338 - 4343. [Abstract] [Full Text] [PDF]