A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80% of early (UICC I) colon cancer stages in humans |
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| Authors: | Bettina Scholtka Mandy Schneider Ralph Melcher Tiemo Katzenberger Daniela Friedrich Kornelia Berghof-Jäger Wolfgang Scheppach Pablo Steinberg |
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| Institution: | 1. Department of Laboratory Medicine and Pathology Mayo Clinic, Hilton 7, 200 1st Street SW, Rochester, MN 55905, USA;2. Department of Medicine, Mayo Clinic 200 1st Street SW, Rochester, MN 55905, USA;1. Department of Heart and Vessels, Cardiac Surgery Unit, Varese University Hospital, Varese, Italy;2. Department of Surgical and Morphological Sciences, Cardiac Surgery Unit, Varese University Hospital, University of Insubria, Varese, Italy;3. Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland;4. Department of Heart and Vessels, Vascular Surgery Unit, Varese University Hospital, Italy;5. Department of Cardiac Surgery, Cardiocentro Ticino, Lugano, Switzerland;1. Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan;2. Division of Laboratory Medicine and Clinical Genetics, Chiba University Hospital, Chiba, Japan;3. Department of Medical Technology and Sciences, International University of Health and Welfare, Fukuoka, Japan;4. Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan;5. Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan;6. Department of Pathology, Chiba University Hospital, Chiba, Japan |
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| Abstract: | Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed. |
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