Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell carcinoma.
The p16 gene encodes a 16-kDa cyclin kinase inhibitor, and the p14ARF gene a 14-kDa protein, which acts as a cell cycle regulator or tumor suppressor in human cancer cells. Both genes are mapped on chromosome 9p21. Previous studies have suggested that the p16 gene has important roles in head and neck squamous cell carcinoma. To clarify carcinogenesis in oral squamous cell carcinoma (OSCC), we examined 44 primary OSCCs for alterations of p16 and p14ARF mRNA expression, the methylation status of the p16 gene promoter, the loss of heterozygosity (LOH) at the 9p21 locus, and p16 and p14ARF gene mutations. Alterations of p16 and p14ARF mRNA expression were seen in 27 (61.4%) of 44 and 10 (22.7%) of 44 of OSCC samples, respectively. Methylation of the p16 gene promoter region was detected in 28 (63.6%) of 44 samples, and LOH at 9p21 locus was found in 30 (68.2%) of 44. p16 and p14ARF gene mutations were observed in 4 (9.0%) of 44 and 2 (4.5%) of 44 samples, respectively. Suspected homozygous deletion (HD) was seen in 9 (20.5%) of 44. All cases except one (97.7%) showed alterations in p16, p14ARF, and their locus. These data indicate that the status of p16 and p14ARF genes in OSCC is frequently influenced by methylation, gene mutation, and allelic deletions. Furthermore, these genes and their 9p21 locus have various roles in the pathogenesis of OSCC.
Ohta
Shinsuke
S
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. shinsuke@med.yokohama-cu.ac.jp
Uemura
Hiroji
H
Matsui
Yoshiro
Y
Ishiguro
Hitoshi
H
Fujinami
Kiyoshi
K
Kondo
Keiichi
K
Miyamoto
Hiroshi
H
Yazawa
Takuya
T
Danenberg
Kathleen
K
Danenberg
Peter V
PV
Tohnai
Iwai
I
Kubota
Yoshinobu
Y
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D020868:Gene Silencing; D019942:Genes, p16; D006801:Humans; D019656:Loss of Heterozygosity; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF