Abstract
Approximately 5-10% of all colorectal carcinomas arise from cancer predisposition syndromes caused by heterozygote germline mutations in post-replicative DNA mismatch repair (MMR) genes. In contrast to gastrointestinal polyposis syndromes, carcinomas in these patients do not occur on the background of increased numbers of polyps and hence are refered to as hereditary non-polyposis colorectal cancers (HNPCC). Six different MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3 and PMS2, have been identified in the human genome. In the majority of HNPCC patients, heterozygote germline mutations are present in the MSH2 or MLH1 gene. Detection of mutations by conventional sequencing technology is expensive and labor intensive due to the complex intron and/or exon structures. In this study, we therefore have explored whether capillary electrophoresis-based single strand conformation polymorphism (SSCP-CE) provides a reliable means for mutation screening. We have tested different MLH1 mutations in exons 9 and 16 and find that SSCP-CE produces reliable electrophoretic patterns that allow recognition of wild-type alleles, microdeletions and point mutations. In summary, SSCP-CE provides a rapid, automated, and cost-effective technology for MSH2 and MLH1 mutation screening and will facilitate genetic diagnostics for HNPCC patients.
Combinatorial Chemistry & High Throughput Screening
Title: High Throughput Genetic Screening for the Detection of Hereditary Nonpolyposis Colon Cancer (HNPCC) Using Capillary Electrophoresis
Volume: 3 Issue: 6
Author(s): Sabine Merkelbach-Bruse, Sema Kose, Inge Losen, Anja-Katrin Bosserhoff and Reinhard Buettner
Affiliation:
Abstract: Approximately 5-10% of all colorectal carcinomas arise from cancer predisposition syndromes caused by heterozygote germline mutations in post-replicative DNA mismatch repair (MMR) genes. In contrast to gastrointestinal polyposis syndromes, carcinomas in these patients do not occur on the background of increased numbers of polyps and hence are refered to as hereditary non-polyposis colorectal cancers (HNPCC). Six different MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3 and PMS2, have been identified in the human genome. In the majority of HNPCC patients, heterozygote germline mutations are present in the MSH2 or MLH1 gene. Detection of mutations by conventional sequencing technology is expensive and labor intensive due to the complex intron and/or exon structures. In this study, we therefore have explored whether capillary electrophoresis-based single strand conformation polymorphism (SSCP-CE) provides a reliable means for mutation screening. We have tested different MLH1 mutations in exons 9 and 16 and find that SSCP-CE produces reliable electrophoretic patterns that allow recognition of wild-type alleles, microdeletions and point mutations. In summary, SSCP-CE provides a rapid, automated, and cost-effective technology for MSH2 and MLH1 mutation screening and will facilitate genetic diagnostics for HNPCC patients.
Export Options
About this article
Cite this article as:
Merkelbach-Bruse Sabine, Kose Sema, Losen Inge, Bosserhoff Anja-Katrin and Buettner Reinhard, High Throughput Genetic Screening for the Detection of Hereditary Nonpolyposis Colon Cancer (HNPCC) Using Capillary Electrophoresis, Combinatorial Chemistry & High Throughput Screening 2000; 3 (6) . https://dx.doi.org/10.2174/1386207003331409
DOI https://dx.doi.org/10.2174/1386207003331409 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Metastatic Colorectal Cancer: Role of Target Therapies and Future Perspectives
Current Cancer Drug Targets Preface
Current Medicinal Chemistry - Anti-Cancer Agents β -Glucans and their Applications in Cancer Therapy: Focus on human studies
Anti-Cancer Agents in Medicinal Chemistry Chemical Analysis of the Chinese Herbal Medicine Turmeric (Curcuma longa L.)
Current Pharmaceutical Analysis Antimicrobial and Chemopreventive Properties of Herbs and Spices
Current Medicinal Chemistry Anti-Tumor Mechanisms of Novel 3-(4-Substituted Benzyl)-5-Isopropil-5- Phenylhydantoin Derivatives in Human Colon Cancer Cell Line
Anti-Cancer Agents in Medicinal Chemistry Anti-Cancer Compounds from Terrestrial and Marine Resources -In silico and Experimental Studies
Current Computer-Aided Drug Design Anticarcinogenic Actions of Tributyrin, A Butyric Acid Prodrug
Current Drug Targets Esophagogastric Cancer: Integration of Targeted Therapies into Systemic Chemotherapy
Current Cancer Drug Targets Meet Our Editorial Board Member:
Reviews on Recent Clinical Trials Damnacanthal: A Promising Compound as a Medicinal Anthraquinone
Anti-Cancer Agents in Medicinal Chemistry PPAR-Gamma in Ulcerative Colitis: A Novel Target for Intervention
Current Drug Targets Use of Biguanides and the Risk of Colorectal Cancer: A Register-Based Cohort Study
Current Drug Safety Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor Inhibitors as Anti-Angiogenic Agents in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Epigenetic Remodeling of Chromatin Architecture: Exploring Tumor Differentiation Therapies in Mesenchymal Stem Cells and Sarcomas
Current Stem Cell Research & Therapy Current Concepts and Future Directions in Radioimmunotherapy
Current Drug Discovery Technologies Serum Carboxypeptidase N1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Cell Arrest and Apoptosis Induced by the Next Generation of Vanadium Based Drugs: Action Mechanism to Structure Relation and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Epigenetic Mechanisms Underlying Diet-Sourced Compounds in the Prevention and Treatment of Gastrointestinal Cancer
Anti-Cancer Agents in Medicinal Chemistry Peptido-Targeting of the Mitochondrial Transition Pore Complex for Therapeutic Apoptosis Induction
Current Pharmaceutical Design