p53 missense but not truncation mutations are associated with low levels of p21CIP1/WAF1mRNA expression in primary human sarcomas

Abstract

Summary 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.

Proximal‐type epithelioid sarcoma in a 36‐year‐old man: Closer immunoelectron‐microscopic resemblance of the tumor cells to epithelial cells than to mesenchymal cells

“…reported that some sarcomas showed WAF1 over-expression without p53 alteration. 19 Although we did not analyze the level of WAF1 messenger RNA, the current patient's tumor cells are thought to be similar to a type reported by Mousses et al . 19 Proximal-type epithelioid sarcoma is a relatively rare soft tissue tumor.…”

Primary proximal epithelioid sarcoma of the lung successfully treated with pneumonectomy and adjuvant chemotherapy

“…There may be similar pathological mechanisms in the development of epithelioid tumours as well. Some studies that examined the role of P53 mutations did not find good evidence for direct involvement of either the P53 or P21 pathway in tumourigenesis 8 9. It is very difficult to examine the relationship between HIV infection and the incidence of extremely rare cancers.…”