title: Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening in MSH2 and MLH1 genes.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a deficiency in DNA mismatch repair in consequence of germline mutations mainly in the genes MSH2 and MLH1. Around 10% of patients suspected of HNPCC are identified with large genomic deletions that cannot be detected by conventional methods of mutation screening. The recently developed multiplex ligation-dependent probe amplification (MLPA) proved to be an easy to perform method for deletion detection and is reliable when more than one exon is deleted. We show that, in some cases, apparent deletions of single exons may actually result from single base substitutions or small insertions/deletions in the hybridisation sequence of MLPA probes. We conclude that single exon deletions, detected by MLPA or multiplex PCR, should be validated with additional methods.
authors.affiliation: Institute of Human Genetics, University of Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Wehner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Marlies
authors.initials: M
authors.lastname: Sengteller
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Friedrichs
authors.forename: Stefan
authors.initials: S
authors.lastname: Aretz
authors.forename: Waltraut
authors.initials: W
authors.lastname: Friedl
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Constanze
authors.initials: C
authors.lastname: Pagenstecher
mesh_terms: D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D004260:DNA Repair / Q000235:genetics; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein