title: [Molecular diagnosis and clinical consequences in families with HNPCC syndrome].
abstract: Thirteen families were included in our HNPCC surveillance program, eight of which met strict and three incomplete Amsterdam criteria. Two index patients were younger than 35 years of age. Tumors of all index persons showed microsatellite instabilities in at least 50% of the ten markers studied. Immunohistochemical analysis of tumor sections was performed using antibodies against hMLH1 and hMSH2 proteins in order to identify the mutated gene, which is not expressed in the tumor. Coding regions of hMLH1 and hMSH2 genes were amplified by PCR from genomic DNA and sequenced. In nine families pathogenetic mutations all resulting in a truncated protein, could be identified. Furthermore, 21 intron and exon polymorphisms were found. Since July 1997 we have offered surgical and genetic counseling to families with hereditary cancer syndromes in a special outpatient clinic. In addition to 13 index patients three asymptomatic gene carriers were included and eight noncarriers were excluded from the HNPCC surveillance program, as recommended by the HNPCC study group of Germany. Molecular diagnosis has considerable clinical implication in hereditary nonpolyposis colorectal cancer (HNPCC) families with respect to family members who actually have the disease as well as gene carriers and noncarriers.
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005820:Genetic Testing; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein