title: High proportion of large genomic rearrangements in hMSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families of the Basque Country.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC), which represents the most common form of inherited colorectal cancer, results from germline alterations of the mismatch repair genes MSH2, MLH1 and MSH6. Rearrangements of MSH2 and MLH1 are involved in at least 10% and 4.3%, respectively, of the HNPCC families fulfilling the Amsterdam (AMS) criteria. We applied a recently developed method, multiplex ligation-dependent probe amplification (MLPA), to study MLH1/MSH2 copy number changes in 29 unrelated Basque Country HNPCC families. We detected six different genomic rearrangements in total (6/29=20.69%), four in MSH2 gene (13.79%), and two in MLH1 gene. All of the MSH2 rearrangements were genomic deletions involving several exons. The MLH1 rearrangements were initially detected as one deletion of exon 18 and one deletion of exon 19, but after sequencing analysis, these deletions were not confirmed and corresponded to base pair mutations. We conclude that MLPA is an excellent tool for detecting exon copy number changes in MLH1 and MSH2 in the DNA from HNPCC patients, although all detected rearrangements should be confirmed by an independent molecular methodology. Furthermore, our results in the Basque Country show higher percentages of rearrangements than previously published by other authors.
authors.affiliation: Molecular Genetics Laboratory, Hospital de Cruces, Plaza de Cruces s/n, 48903-Barakaldo-Bizkaia, Spain. cmbouzas@universia.es
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: Enrique
authors.initials: E
authors.lastname: Ojembarrena
authors.forename: Elena
authors.initials: E
authors.lastname: Beristain
authors.forename: Javier
authors.initials: J
authors.lastname: Errasti
authors.forename: Noelia
authors.initials: N
authors.lastname: Viguera
authors.forename: Maria-Isabel
authors.initials: MI
authors.lastname: Tejada Minguéz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D015342:DNA Probes / Q000737:chemistry; D005091:Exons / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013030:Spain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015342:DNA Probes; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein