The finding of both chromosomal deletions of 17p and p53 mutation indicates that these changes may take place early in the process of lung carcinogenesis.
The p53 tumor suppressor gene is of particular interest because the relationship between environmental factors and genetic alterations of carcinogenesis can be investigated.
Despite extensive data linking mutations in the p53 gene to human tumorigenesis, little is known about the cellular regulators and mediators of p53 function.
These findings suggest that mutational inactivation of the p53 gene is infrequent but is involved in the tumorigenesis of several types of haematologic neoplasms at least in some cases.
Extremely frequent p53 gene mutations indicated that the mutations are likely be intimately involved in the carcinogenesis of oral squamous cell carcinoma.
These results are consistent with the hypothesis that certain mutations in p53 may function in multistage lung carcinogenesis by reducing the responsiveness of bronchial epithelial cells to negative growth factors.
Participation of p53 in this pathway suggests a mechanism for the contribution of abnormalities in p53 to tumorigenesis and genetic instability and provides a useful model for studies of the molecular mechanisms of p53 involvement in controlling the cell cycle.
The pattern of mutation in the p53 gene differs among cancers and may be a useful epidemiological tool for identification of factors contributing to carcinogenesis.
These results suggest that p53 inactivation is not a necessary component of nasopharyngeal carcinogenesis in Cantonese but may be important in the establishment of cell lines derived from these tumors.
The availability of p53 knockout mice generated by gene targeting has enabled us to investigate the functional role of the p53 tumor suppressor gene in initiation, promotion, and progression of carcinogenesis in vivo, using mouse skin as a model system.
The results indicate that the TP53 gene is involved in the tumorigenesis of several sarcoma subtypes in a higher fraction of cases than was previously recognized.
To assess the role of p53 in HPV-associated genital carcinogenesis, the expression of p53 protein was studied immunohistochemically in 22 genital carcinomas and precancer lesions; 8 vulvar carcinomas, 1 VIN (vulvar intraepithelial neoplasia), 5 cervical carcinomas and 8 CIN (cervical intraepithelial neoplasia) using monoclonal antibody PAb 1801.
Thus, single p53 mutation seems to occur in initial stages of astrocytoma tumorigenesis; the later lost of the remaining wild-type allele appears associated with the progression towards a more malignant stage.
We have recently demonstrated that human papillomavirus type 18 (HPV-18) E6 can partially overcome the growth-suppressive effects of wt p53, but it remains unclear what role p53 plays in cervical carcinogenesis.
These findings demonstrate that oncogenic E6 can disrupt an important cellular response to DNA damage mediated by p53 and may contribute to the subsequent accumulation of genetic changes associated with cervical tumorigenesis.
A strong association (P = 0.0015) was found between deletions on chromosome region 17p13.3 and p53 mutations suggesting that loss of the wild-type p53 allele might be necessary for tumorigenesis.