caa a22 4500 397574215 CHVBK 20180308164850.0 cr unu---uuuuu 161202e199606 xx s 000 0 eng 10.1093/hmg/5.6.763 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.6.763 DNA Mismatch Repair Gene Mutations in 55 Kindreds with Verified Or Putative Hereditary Non-Polyposis Colorectal Cancer [Elektronische Daten] [Minna Nyström-Lahti, Ying Wu, Anu-Liisa Moisio, Robert M. W. Hofstra, Jan Osinga, Jukka-Pekka Mecklin, Heikki J. Järvinen, Jaakko Leisti, Charles H. C. M. Buys, Albert de la Chapelle, Päivi Peltomäki] The DNA mismatch repair genes MSH2 and MLH1 have been shown to account for a major share of hereditary non-polyposis colorectal cancer (HNPCC). We searched for germline mutations in these genes in 35 HNPCC kindreds fulfilling the Amsterdam diagnostic criteria and in a further 20 kindreds with an average of four affected members per family but not meeting the formal criteria. We first screened for truncations by reverse transcrip-tase (RT)-PCR. If no mutation was found, we screened genomic DNA by a novel application of two-dimensional (2-D) DNA electrophoresis that allows the simultaneous study of all exons of each gene. All abnormalities were followed up by sequencing. Eight different pathogenic germline mutations were found, two in MSH2 and six in MLH1. We report three major conclusions. First, these mutations together accounted for 86% (30/35) of the kindreds meeting the Amsterdam criteria, but only 30% (6/20) of the remaining kindreds, suggesting differences in etiology. Second, MLH1 was involved in >90% (34/36) of kindreds with a known predisposing mutation, suggesting that mutations in the MLH1gene are responsible for most HNPCC kindreds in Finland. Third, our results indicate that the successive application of RT-PCR and 2-D DNA electrophoresis is a sensitive and efficient method for mutation screening in typical HNPCC. © 1996 Oxford University Press Nyström-Lahti Minna Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut Wu Ying Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut Moisio Anu-Liisa Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut Hofstra Robert M. W. Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut Osinga Jan Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut Mecklin Jukka-Pekka Jyväskylä Central Hospital, FIN-40620 Jyväskylä, Finland aut Järvinen Heikki J. Second Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-40620 Jyväskylä, Finland aut Leisti Jaakko Department of Clinical Genetics, Oulu University Central Hospital, FIN-90220 Oulu, Finland aut Buys Charles H. C. M. Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut de la Chapelle Albert Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut Peltomäki Päivi Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut Human Molecular Genetics Oxford University Press 5/6(1996-06), 763-769 0964-6906 5:6<763 1996 5 hmg https://doi.org/10.1093/hmg/5.6.763 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.6.763 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nyström-Lahti Minna Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut NATIONALLICENCE 700 1- Wu Ying Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut NATIONALLICENCE 700 1- Moisio Anu-Liisa Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut NATIONALLICENCE 700 1- Hofstra Robert M. W. Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut NATIONALLICENCE 700 1- Osinga Jan Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut NATIONALLICENCE 700 1- Mecklin Jukka-Pekka Jyväskylä Central Hospital, FIN-40620 Jyväskylä, Finland aut NATIONALLICENCE 700 1- Järvinen Heikki J. Second Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-40620 Jyväskylä, Finland aut NATIONALLICENCE 700 1- Leisti Jaakko Department of Clinical Genetics, Oulu University Central Hospital, FIN-90220 Oulu, Finland aut NATIONALLICENCE 700 1- Buys Charles H. C. M. Department of Medical Genetics, Rijksuniversiteit Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands aut NATIONALLICENCE 700 1- de la Chapelle Albert Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut NATIONALLICENCE 700 1- Peltomäki Päivi Department of Medical Genetics, Haartman Institute, P.O. Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014 Helsinki, Finland aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/6(1996-06), 763-769 0964-6906 5:6<763 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford