Promoter methylation of p16INK4a, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma.
BACKGROUND
Promoter methylation is a common mechanism of inactivation of tumor suppressor genes in multiple tumor types. However, little is known about its role in the development of adenoid cystic carcinoma of the salivary gland (ACC). In the current study, the authors investigated whether promoter methylation is common in ACC and whether it may influence ACC development.


METHODS
The promoter methylation status of the genes p16(INK4a), RASSF1A, DAPK, and MGMT, which are important in cell growth regulation, apoptosis, and DNA repair, was determined in tissue sections of tumor samples from 60 patients with ACC using methylation-specific polymerase chain reaction. The association between methylation status and patients' clinical and pathologic characteristics were assessed.


RESULTS
Of the 60 tumors, DNA methylation of the p16(INK4a) promoter was detected in 28 tumors (47%); the respective values DNA methylation of the RASSF1A, DAPK, and MGMT promoters were 25 tumors (42%), 16 tumors (27%), and 4 tumors (7%), respectively. Forty-six tumors (77%) had DNA methylation in > or = 1 of the 4 promoters, 20 tumors (33%) had DNA methylation in > or = 2 promoters, 6 tumors (10%) had DNA methylation in > or = 3 promoters, and 1 tumor (2%) had DNA methylation in all 4 promoters. RASSF1A promoter methylation was more frequent in high-grade tumors than in low-grade tumors (P = 0.009), in advanced-stage tumors (P = 0.008), and in tumors with metastasis (P = 0.005).


CONCLUSIONS
Promoter methylation of p16(INK4a), RASSF1A, and DAPK was common in ACC, and it is possible that such methylation may influence the development of ACC. The high frequency of RASSF1A promoter methylation in high-grade tumors and in tumors with metastasis suggested a role for this gene in the progression of ACC.
Li
Jiang
J
College of Stomatology, Shanghai Second Medical University, Shanghai, China.
El-Naggar
Adel
A
Mao
Li
L
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D064550:Death-Associated Protein Kinases; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases