Alterations of the p14ARF-p53-MDM2 pathway in oral squamous cell carcinoma: MDM2 overexpression is a common event.
The majority of global incidences of oral cancer occur in Asia, and the aetiology of oral cancer is different in Asia as it is in the West. However, whereas there is a growing understanding of the molecular mechanisms of oral cancer progression in the West, there is little progress in this understanding in Asia. In particular, the role of the p53 pathway in modulating cancer progression in Asian oral cancer remains unclear. In this study, we micro-dissected and analysed 20 well-differentiated oral squamous cell carcinoma specimens for alterations in the p53 pathway. We found that 6/20 samples contained mutations in the p53 gene which occurred in three hotspots, at codon 203, 218 and 296. Furthermore, 6/20 samples had a homozygous deletion of p14ARF, but notably p14ARF deletion and p53 mutation events were often independent and mutually exclusive. Strikingly, MDM2 was upregulated in 20/20 samples, but not in 3/3 normal tissue specimens. Taken together, these data suggest that inactivation of the p53 pathway is a frequent event in oral squamous cell carcinoma, which occurs by an aberration in one of a number of players in the p53 pathway.
Lim
Kue Peng
KP
Cancer Research Initiatives Foundation (CARIF), Outpatient Centre, Subang Jaya Medical Centre, 47500 Subang Jaya, Selangor, Malaysia.
Sharifah
Hamid
H
Lau
Shin Hin
SH
Teo
Soo-Hwang
SH
Cheong
Sok Ching
SC
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002454:Cell Differentiation; D003062:Codon; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D005091:Exons; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D007194:India; D007834:Lasers; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism*; D009154:Mutation; D031721:Piper betle / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D011312:Pressure; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
D003062:Codon; D017931:DNA Primers; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D004247:DNA; D051736:Proto-Oncogene Proteins c-mdm2