title: The value of multi-modal gene screening in HNPCC in Quebec: three mutations in mismatch repair genes that would have not been correctly identified by genomic DNA sequencing alone.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited cancer syndrome caused by a mutation in one of the mismatch repair genes, most frequently MLH1 or MSH2. The rate of mutation detection is influenced by many factors, including the diagnostic methods used. Large deletions, which occur frequently in MLH1 and MSH2, are not detected by exon-by-exon screening methods. Here, we describe three mutations in mismatch repair genes detected using a screening protocol that combines protein truncation test (PTT) analysis and multiplex ligation-dependent probe amplification (MLPA) with genomic and cDNA sequencing. Two of these mutations consist of large deletions in MLH1 that were detected by both MLPA and PTT but that would have been missed by genomic DNA sequencing. The third is a large deletion in MSH2 that could not be detected by PTT because of its location relative to the primers used to amplify the cDNA, or by sequencing. This mutation was detected by MLPA.
authors.affiliation: Department of Human Genetics, McGill University, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: McVety
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiffault
authors.forename: Philip H
authors.initials: PH
authors.lastname: Gordon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macnamara
authors.forename: Nora
authors.initials: N
authors.lastname: Wong
authors.forename: Karlene
authors.initials: K
authors.lastname: Australie
authors.forename: Lidia
authors.initials: L
authors.lastname: Kasprzak
authors.forename: George
authors.initials: G
authors.lastname: Chong
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics*; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000517:prevention & control; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods*; D016678:Genome; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008297:Male; D018895:Microsatellite Repeats; D051718:MutS Homolog 2 Protein / Q000235:genetics; D016133:Polymerase Chain Reaction; D011322:Primary Prevention / Q000379:methods; D011379:Prognosis; D011792:Quebec / Q000453:epidemiology; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm; D051718:MutS Homolog 2 Protein