Aberrant methylation in promoter regions of cyclin-dependent kinase inhibitor genes in adenoid cystic carcinoma of the salivary gland.
Adenoid cystic carcinoma (ACC) is a common malignant neoplasm of the salivary gland. The mechanism underlying ACC carcinogenesis is not fully elucidated, although data on associated genetic alterations are accumulating. Cyclin-dependent kinase inhibitors (CKIs) act as tumor suppressors in various cancers, and aberrant methylation in the CKI gene promoter region has been linked to gene silencing and downregulation of expression. The present study investigated methylation of CKI genes, p15, p18, p19, p21, and p27, in 34 cases of ACC. We found frequent and plural methylations of these genes in most cases (68.8% in p15, 90.3% in p18, 78.8% in p19, 92.3% in p21, and 26.5% in p27). Cell cycle disruption induced by these epigenetic aberrations might be important in the tumorigenesis of ACC.
Daa
Tsutomu
T
Department of Pathology, Faculty of Medicine, Oita University, Oita, Japan. daatom@med.oita-u.ac.jp
Kashima
Kenji
K
Kondo
Yoshiyuki
Y
Yada
Naomi
N
Suzuki
Masashi
M
Yokoyama
Shigeo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008745:Methylation; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27