TY - JOUR
T1 - Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell carcinoma
AU - Ohta, Shinsuke
AU - Uemura, Hiroji
AU - Matsui, Yoshiro
AU - Ishiguro, Hitoshi
AU - Fujinami, Kiyoshi
AU - Kondo, Keiichi
AU - Miyamoto, Hiroshi
AU - Yazawa, Takuya
AU - Danenberg, Kathleen
AU - Danenberg, Peter V.
AU - Tohnai, Iwai
AU - Kubota, Yoshinobu
N1 - Funding Information:
This work was partially supported by grants-in-aid from the Ministry of Education, Science and Culture of Japan.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.tripleo.2008.08.027
DO - 10.1016/j.tripleo.2008.08.027
M3 - Article
C2 - 19101490
AN - SCOPUS:57649230131
SN - 1079-2104
VL - 107
SP - 81
EP - 91
JO - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology
JF - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology
IS - 1
ER -