Alterations of p14ARF and p16INK4a genes in salivary gland carcinomas.
The p14ARF and p16INK4a genes are localized to 9p21, where genetic alterations have been reported to be frequent in various human neoplasms. To elucidate their status in salivary gland tumorigenesis, we analyzed a series of 36 salivary gland carcinomas (SGCs) using methylation-specific PCR, differential PCR and immunohistochemistry. Homozygous deletion (3 cases) or methylation (7 cases) of p14ARF was detected in 10 (28%) SGCs, one and three showing co-deletion and co-methylation of both p14ARF and p16INK4a genes, respectively. A total of 5 (14%) SGCs demonstrated homozygous deletion (1 case) or methylation (4 cases) of p16INK4a, all but one being adenoid cystic carcinomas. Immunohistochemical study revealed loss of p14ARF and p16INK4a expression in 11 samples (31%), correlating with the gene status. These results indicate that inactivation of p14ARF and p16INK4a genes by either homozygous deletion or promoter hypermethylation may be important for the molecular pathogenesis of salivary malignant tumors, and provide clear evidence that epigenetic changes like methylation are related to salivary gland carcinogenesis.
Nishimine
Masayoshi
M
Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Nakamura
Mitsutoshi
M
Kishi
Munehiro
M
Okamoto
Masumi
M
Shimada
Keiji
K
Ishida
Eiwa
E
Kirita
Tadaaki
T
Konishi
Noboru
N
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019942:Genes, p16; D006720:Homozygote; D006801:Humans; D007124:Immunoenzyme Techniques; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF