A study on MSH2 and MLH1 mutations in hereditary nonpolyposis colorectal cancer families from the Basque Country, describing four new germline mutations.
Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome underlies between 2 and 5% of all colorectal cancer. It is inherited as an autosomal dominant condition due to mutations in the mismatch repair genes. Fifty-four non-related index cases, 21 of them fulfilling Amsterdam criteria I or II, were studied. Ten (10/21 = 47.6%) different pathological mutations were found in this group, two of which had not previously been reported--one in MLH1 and the other in MSH2-. In the remaining patients, we also found another family with one of these new mutations, and four additional changes, two of which were also new--a pathological change in MSH2 and a second change of uncertain significance in MLH1-, while the other two changes had already been reported. Of all mutations, eight were found in MSH2 (8/15 = 53.3%) and seven in MLH1 (7/15 = 46.6%), suggesting a slightly greater involvement of MSH2 in HNPCC than MLH1 in our population, in contrast to the results reported by other authors.
Martínez-Bouzas
Cristina
C
Laboratorio de Genética Molecular, Servicio de Bioquímica, Hospital de Cruces, 48903 Barakaldo-Bizkaia, Spain. cmbouzas@universia.es
Beristain
Elena
E
Ojembarrena
Enrique
E
Errasti
Jose
J
Mujika
Karmele
K
Viguera
Noelia
N
Tejada
Maria Isabel
MI
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein