Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer.
BACKGROUND
Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer.


METHODS
Microsatellite instability and promoter methylation were investigated by PCR, denaturing-polyacrylamide gel electrophoresis and digestion with methylation-specific restriction enzymes.


RESULTS
Microsatellite instability was observed in 41% of the patients. hMLH1 and hMSH2 genes were methylated in 47% and 30% of the patients, respectively. BAT25 and BAT26 instability were associated with age and histopathology, respectively. Methylation frequency of the hMLH1 gene promoter was significantly higher in patients displaying a high level of microsatellite instability. Instability at the BAT 26 and D2S123 loci were associated with the MSI-high status.


CONCLUSIONS
Our results indicate that microsatellite instability and modifications in the hMLH1 and hMSH2 genes are implicated in a significant proportion of the patients with head and neck cancer.
Oncology Institute, Department of Basic Oncology, Istanbul Medical Faculty, Department of Otorhinolaryngology, Istanbul University, Turkey.
S
S
Demokan
Y
Y
Suoglu
D
D
Demir
M
M
Gozeler
N
N
Dalay
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D020137:Base Pair Mismatch; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D004260:DNA Repair; D049914:DNA Repair-Deficiency Disorders; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017931:DNA Primers; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein