Discordance between K-ras mutations in bone marrow micrometastases and the primary tumor in colorectal cancer
| Autor: | Marc A. Reymond, Hans Lippert, Werner Schlegel, Miguel A. Peinado, Peter Stosiek, Ralf Steinert, M. Hantschick, Silvia Tortola, Ingo Gastinger |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Genotype Colorectal cancer DNA Mutational Analysis medicine.disease_cause Polymerase Chain Reaction Metastasis medicine Humans Prospective Studies Codon Aged Mutation business.industry Micrometastasis DNA Neoplasm Middle Aged medicine.disease Neoplastic Cells Circulating Primary tumor Clone Cells medicine.anatomical_structure Cell Transformation Neoplastic Genes ras Oncology Immunohistochemistry Female Bone marrow business Bone Marrow Neoplasms Colorectal Neoplasms |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0732-183X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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