These results indicate that inactivation of the p53 gene through mutations and the allelic deletion may play an important role in gastric tumorigenesis.
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.
A previous report using cervical carcinoma cell lines suggests that the inactivation of two tumor suppressor gene products, p53 and pRB, either by complex formation with the E6 and E7 proteins of oncogenic human papillomaviruses (HPVs) or by mutation, may be an important step in cervical carcinogenesis (M. Scheffner et al., Proc.Natl.Acad.Sci.USA, 88: 5523-5527, 1991).
The discovery of the tumor suppressor genes, for which loss of function mutations are oncogenic as in the RB gene of the retinoblastoma and p53 gene, has introduced a new concept of oncogenesis which could be useful even in the cure of the neoplasms.
These observations further support the notion that germline p53 mutation plays a key role in the tumorigenesis of individuals with Li-Fraumeni syndrome.
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 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter.
We conclude that p53 overexpression is one of the most common abnormalities identified in head and neck cancer, and may be a useful marker in the study of multistep progression of tumorigenesis.
On the basis of a previous report that genes on chromosome 17p were not deleted in MTCs and were relatively infrequently deleted in pheochromocytomas, our results suggest that the p53 gene is not involved in tumorigenesis of MTC or pheochromocytoma.
The p53 tumor suppressor gene is of particular interest because the relationship between environmental factors and genetic alterations of carcinogenesis can be investigated.
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.
Based upon these results, we concluded that the p53 gene may play a role in the tumorigenesis of a limited number of parathyroid adenoma and thyroid cancers, and that the p53 mutation with an allelic loss of the p53 gene is an important factor in malignant tumorigenesis of the thyroid gland.
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.
Extremely frequent p53 gene mutations indicated that the mutations are likely be intimately involved in the carcinogenesis of oral squamous cell carcinoma.
Despite extensive data linking mutations in the p53 gene to human tumorigenesis, little is known about the cellular regulators and mediators of p53 function.
We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in less than 10% of NPC cases.