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

Abstract

Many growth-suppressing signals converge to control the levels of the CDK inhibitor p21(CIP1/WAF1). Some human cancers exhibit low levels of expression 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 to 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 group 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 mutations predicted to result in truncation of the p53 protein. The results of this study suggest that different types of p53 mutations can have different effects on the expression of downstream genes such as p21(CIP1/WAF1) in human sarcomas.