p53 missense but not truncation mutations ave associated with low levels of p21(CIP1/WAF1) mRNA expression in primary human sarcomas

Many growth-suppressing signals converge to control the levels of the CDK i nhibitor p21(CIP1/WAF1). Some human cancers exhibit low levels of expressio n of p21(CIP1/WAF1) and mutations in p53 have been implicated in this down- regulation. To evaluate whether the presence of p53 mutations was related t o the in vivo expression of p21(CIP1/WAF1) mRNA in sarcomas we measured the p21(CIP1/WAF1) mRNA levels for a group of 71 primary bone and soft tissue tumours with known p53 status. As expected, most tumours with p53 mutations expressed low levels of p21(CIP1/WAF1) mRNA. However, we identified a grou p of tumours with p53 gene mutations that exhibited normal or higher levels of p21(CIP1/WAF1) mRNA. The p53 mutations in the latter group were not the common missense mutations in exons 4-9, but were predominantly nonsense mu tations predicted to result in truncation of the p53 protein. The results o f this study suggest that different types of p53 mutations can have differe nt effects on the expression of downstream genes such as p21(CIP1/WAF1) in human sarcomas. (C) 2001 Cancer Research Campaign.