title: The impact of molecular diagnosis on familial colorectal cancer.
abstract: We have shown the impact of molecular diagnostics related to mutation detection in an extensive family with a strong history of colorectal cancer. The nature and presentation of the cancers suggested that hereditary nonpolyposis colorectal cancer was the most likely cause. The strategies employed have enabled the detection and characterisation of the causative mutation in the proband and predictive testing in the remaining relatives where requested. Using the chemical cleavage of mismatches technique and direct sequencing, the MSH2 and MLH1 genes of the proband were investigated. A single base substitution, C-->T at nucleotide 350, codon 117, of the MLH1 gene was identified. Across the family pedigree at specific points, 22 other relatives have been tested for the mutation by direct DNA sequencing from genomic DNA. Of the total of 23 patients tested to date, 11 have the mutation. In conjunction with appropriate genetic counselling, this service has clarified the genetic status of many individuals within this family. Predictive information provided prior to the development of symptoms enables individuals to make informed choices regarding disease management and the future, removing the anxiety associated with the unknown.
authors.affiliation: Molecular Pathology Unit, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Bennett
authors.forename: Z
authors.initials: Z
authors.lastname: Rudzki
authors.forename: S
authors.initials: S
authors.lastname: Cole
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.forename: G
authors.initials: G
authors.lastname: Suthers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005260:Female; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017931:DNA Primers; 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