High frequency of homozygous deletion and methylation of p16(INK4A) gene in oral squamous cell carcinomas.
p16(INK4A) inactivation was analyzed in ten squamous cell carcinoma (SCC) cell lines and 32 primary SCCs, using the polymerase chain reaction (PCR), PCR-single-strand conformation polymorphism, methylation-specific PCR, and cycle sequencing. In the study of cell lines, we detected three deletions in exon 1alpha and exon 2, and detected two methylations. Among tumor samples, we detected the homozygous deletions (HDs) of 43.8% in exon 1alpha 34.4% in exon 2, and methylation was found in 50.0%. The lack of p16(INK4A) with immunohistochemistry was detected in 71.9% and matched the alteration of p16(INK4A) gene. These results suggest that p16(INK4A) inactivation is predominantly caused by HD and methylation, and immunohistochemical evaluation of p16(INK4A) is a useful method.
Nakahara
Y
Y
Department of Oral and Maxillofacial Surgery II, Okayama University Dental School, 2-5-1 Shikata, Okayama 700-8525, Japan. nakahara@dent.okayama-u.ac.jp
Shintani
S
S
Mihara
M
M
Ueyama
Y
Y
Matsumura
T
T
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008441:Maxillary Neoplasms / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16