Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach
| Autor: | Johan J.P. Gille, Charlotte J. Dommering, Jan P. Schouten, D. de Jong, Cathal J. McElgunn, J Th Wijnen, R J van Schooten, Gerard Pals, Gerrit A. Meijer, Fred H. Menko, M. E. Craanen, Petra M. Nederlof, Frans B. L. Hogervorst |
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| Přispěvatelé: | Human genetics, Pathology, Gastroenterology and hepatology |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Male
Cancer Research congenital hereditary and neonatal diseases and abnormalities DNA Repair Base Pair Mismatch HNPCC genomic deletions Biology MLH1 medicine.disease_cause Polymerase Chain Reaction Germline Cohort Studies Germline mutation Proto-Oncogene Proteins Multiplex polymerase chain reaction medicine Humans Multiplex Family neoplasms Germ-Line Mutation Adaptor Proteins Signal Transducing Genetics Mutation Nuclear Proteins nutritional and metabolic diseases Genetics and Genomics Colorectal Neoplasms Hereditary Nonpolyposis digestive system diseases Neoplasm Proteins Pedigree MSH6 DNA-Binding Proteins MutS Homolog 2 Protein Oncology Muir–Torre syndrome MSH2 Female mismatch-repair Carrier Proteins Colorectal Neoplasms MutL Protein Homolog 1 Gene Deletion |
| Zdroj: | Gille, J J P, Hogervorst, F B L, Pals, G, Wijnen, J T, van Schooten, R J, Dommering, C J, Meijer, G A, Craanen, M E, Nederlof, P M, de Jong, D, McElgunn, C J, Schouten, J P & Menko, F H 2002, ' Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach ', British Journal of Cancer, vol. 87, no. 8, pp. 892-7 . https://doi.org/10.1038/sj.bjc.6600565 British Journal of Cancer, 87(8), 892-7. Nature Publishing Group British Journal of Cancer |
| ISSN: | 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600565 |
| Popis: | Hereditary non-polyposis colorectal cancer is an autosomal dominant condition due to germline mutations in DNA-mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Here we describe the application of a novel technique for the detection of genomic deletions in MLH1 and MSH2. This method, called multiplex ligation-dependent probe amplification, is a quantitative multiplex PCR approach to determine the relative copy number of each MLH1 and MSH2 exon. Mutation screening of genes was performed in 126 colorectal cancer families selected on the basis of clinical criteria and in addition, for a subset of families, the presence of microsatellite instability (MSI-high) in tumours. Thirty-eight germline mutations were detected in 37 (29.4%) of these kindreds, 31 of which have a predicted pathogenic effect. Among families with MSI-high tumours 65.7% harboured germline gene defects. Genomic deletions accounted for 54.8% of the pathogenic mutations. A complete deletion of the MLH1 gene was detected in two families. The multiplex ligation-dependent probe amplification approach is a rapid method for the detection of genomic deletions in MLH1 and MSH2. In addition, it reveals alterations that might escape detection using conventional diagnostic techniques. Multiplex ligation-dependent probe amplification might be considered as an early step in the molecular diagnosis of hereditary non-polyposis colorectal cancer. British Journal of Cancer (2002) 87, 892–897. doi:10.1038/sj.bjc.6600565 www.bjcancer.com © 2002 Cancer Research UK |
| Databáze: | OpenAIRE |
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