Inactivation of the p14(ARF), p15(INK4B) and p16(INK4A) genes is a frequent event in human oral squamous cell carcinomas.
The p14(ARF), p15(INK4B) and p16(INK4A) genes were localized to 9p21, where genetic alterations have been reported frequently in various human tumors. We performed a molecular analysis of the mechanism of inactivation in cell lines and 32 oral squamous cell carcinoma (OSCC), using deletion screening, PCR-SSCP, methylation-specific-PCR and cycle sequencing. We detected homozygous deletion of p14(ARF)-1Ebeta in 9 (26.5%), of p15(INK4B) in one (3.1%), and of p16(INK4A) in 22 (56.3%) tumor samples. Three mutations were detected in the p16(INK4A) genes. We detected aberrant methylation of the p14(ARF) genes in 14 (43.8%), of the p15(INK4B) gene in 9 (28.1%), and of the p16(INK4A) gene in 16 (50.0%) tumor samples. Altogether, 87.5% of the samples harbored at least one of the alterations in the p14(ARF), p15(INK4B), and p16(INK4A) genes, indicating that the frequent inactivation of these genes may be an important mechanism during OSCC development.
Shintani
S
S
Department of Oral and Maxillofacial Surgery II, Okayama University Dental School, 2-5-1 Shikata, 700-8525, Okayama, Japan. satoru@m.ehime-u.ac.jp
Nakahara
Y
Y
Mihara
M
M
Ueyama
Y
Y
Matsumura
T
T
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D017353:Gene Deletion; D020868:Gene Silencing; D006720:Homozygote; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins