Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer

• Published in: Annals of oncology Vol. 17; no. 6; pp. 995 - 999
• Main Authors: Demokan, S., Suoglu, Y., Demir, D., Gozeler, M., Dalay, N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-2006; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adaptor Proteins, Signal Transducing; Aged; Antineoplastic agents; Base Pair Mismatch; Base Sequence; Biological and medical sciences; Carcinoma, Squamous Cell - genetics; Carrier Proteins - genetics; DNA Methylation; DNA Primers; DNA Repair; DNA Repair-Deficiency Disorders; Female; head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; hMLH1; hMSH2; Humans; Laryngeal Neoplasms - genetics; Male; Medical sciences; methylation; microsatellite instability; Microsatellite Repeats; Middle Aged; MutL Protein Homolog 1; MutS Homolog 2 Protein - genetics; Neoplasm Staging; Nuclear Proteins - genetics; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Polymerase Chain Reaction; Promoter Regions, Genetic; Tumors; microsatellite instability; head and neck cancer; hMSH2; hMLH1; methylation; Base mismatching; Microsatellite DNA; ENT disease; Instability; Head and neck cancer; Malignant tumor; Methylation; DNA repair; Repair gene
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdl048

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