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Promoter methylation of p16 INK4a , RASSF1A , and DAPK is frequent in salivary adenoid cystic carcinoma
Author(s) -
Li Jiang,
ElNaggar Adel,
Mao Li
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21215
Subject(s) - dna methylation , methylation , promoter , cancer research , biology , tumor suppressor gene , microbiology and biotechnology , cancer , gene , carcinogenesis , gene expression , genetics
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 ≥ 1 of the 4 promoters, 20 tumors (33%) had DNA methylation in ≥ 2 promoters, 6 tumors (10%) had DNA methylation in ≥ 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. Cancer 2005. © 2005 American Cancer Society.