These observations provide strong support for the inclusion of the p53 locus in the group of loci whose functional inactivation by either dominant or recessive modes plays a significant role in human cancer.
The nuclear protein p53 has been reported to be associated with cell transformation and/or proliferation so that the study of p53 expression in human malignancy has potentially important clinical implications.
The fact that P53 gene mutations occurred more often in patients with 17p monosomy seems to support the "recessive" model of tumor suppressive activity of the P53 gene rather than the "dominant" model, in which alteration of only one allele is sufficient for the development of malignancy.
Its location extends the region of the p53 gene where inherited mutations predisposing to cancer are observed and suggests that their distribution may be diverse.
A new technique for characterizing somatic mutations in very small samples of cellularly heterogeneous human cancer tissue was developed and tested using mutations in the p53 gene in breast carcinomas as a model system.
These findings represent one of the highest incidences of this oncogenic mutation yet recorded in a human malignancy and support the concept that p53 may have a functional role in development of the metastatic tumor phenotype.
In particular, the discovery of tumor suppressor gene syndromes, such as Rb1 gene and p53 gene defects manifested in "cancer families," were made possible by their association with sarcomas, otherwise rare tumors.
The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited.
Overexpression of the nuclear phosphoprotein p53 is one of the most frequently detected abnormalities in human cancer and appears to be associated with mutation of the p53 gene.
Overexpression of the nuclear phosphoprotein p53 is one of the most common abnormalities in primary human cancer and appears to be due to point mutation within a highly conserved region of the p53 gene which then encodes for a mutant, more stable protein.
Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
Mutation of the p53 gene was detected in 19 (31%) of 62 cases of cancer of the uterine corpus and was more frequent in groups at an advanced clinical stage and/or with aggressive histology.
In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells.
Recent evidence has implicated germ-line mutations of the p53 gene as the cause of cancer susceptibility in the Li-Fraumeni syndrome, associated with the development of breast cancer and other neoplasms.
New germline mutations of the p53 gene are rare among patients with "sporadic" sarcoma but may be common in patients with sarcoma whose background includes either multiple primary cancers or a family history of cancer.
We suggest that this phenotype defines a new inherited cancer susceptibility syndrome that is distinct from the germ-line mutations in p53 found in some Li-Fraumeni families.
Our data suggest that p53 gene mutations are commonly involved in oral cancer but are neither sufficient nor necessary for the development of malignancy.
Absence of p53 mutations in 36% of the tumors with one 17p allele suggests that a tumor suppressor gene other than p53 may be located on chromosome 17p and involved in progression to malignancy of some gliomas.
Our results show that scattered point mutations in p53 are not uncommon in hepatocellular carcinoma samples from Taiwan and may be important in the development of this cancer.