Abnormalities of the ARF-p53 pathway in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is associated with heavy smoking and dr inking, but the molecular pathway of tumorigenesis is not understood. Inact ivation of the p53 tumor suppressor gene is likely to play an important rol e since p53 mutation is frequently found. The p14ARF tumor suppressor gene is functionally linked to p53, because it is activated by oncogenes and cau ses p53-dependent growth arrest and apoptosis, The relationship between p14 ARF and p53 inactivation has not been described for OSCC, We studied 25 cas es of OSCC to determine if there is an inverse correlation between p53 muta tion and p14ARF inactivation by homozygous deletion or mutation. p53 mutati on was found in 16 of 25 cases (64%), including nine missense and seven tru ncating mutations, While all cases with missense mutations showed abnormal accumulation of p53 protein, there were also five carcinomas which showed i ncreased p53 staining in the absence of mutation. p14ARF deletion or mutati on was found in eight cases (32%), six of which also demonstrated p53 mutat ion. Our findings indicate that OSCC often involves loss of both p14ARF and p53 function and suggest that inactivation of these two tumor suppressor g enes are not functionally equivalent during tumorigenesis.