Germ-line mutations of the tumor-suppressor gene p53 have been observed in some families with the Li-Fraumeni syndrome (LFS), a familial cancer syndrome in which affected relatives develop a diverse set of early-onset malignancies including breast carcinoma, sarcomas, and brain tumors.
Germ-line p53 mutations are associated with dominantly inherited Li-Fraumeni syndrome (LFS), which features early-onset sarcomas of bone and soft tissues, carcinomas of the breast and adrenal cortex, brain tumors, and acute leukemias.
The observation that somatic p53 mutations in sporadic brain tumours are largely restricted to those of astrocytic origin and that astrocytomas also prevail among CNS neoplasms associated with p53 germline mutation strongly suggests, that p53 mutations are capable of initiating neoplastic transformation in astrocytes of the human nervous system.
Finally, while data on the p53 gene and protein studies in human brain tumors are accumulating rapidly, the clinical significance of such data remains unclear.
To prove these data, the authors screened a series of 42 astrocytic human brain tumors with a relatively high proportion (16.6%) of the pilocytic variant for the presence of p53 mutations, using the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis, followed by DNA sequencing.
Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response.
We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements.
By removing alkyl groups from the O6-position in guanine, MGMT can prevent G:C to A:T transition mutations, a type of variation frequently involving TP53 mutations in brain tumors.
The effect of p53 status on response to TMZ was explored in traditional glioma cell lines (U87MG, U251MG, U343MG, U373MG, SF767, LN443 and LNZ308) and brain tumor initiating cells (BTICs--BT012, BT025, BT042, BT048, BT060 and BT069) in two ways: (1) inhibition of p53 by RNAi and (2) sensitivity in relation to intrinsic p53 status, either wild-type or mutant.
Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults.
Initially, a TP53 gene germline missense mutation was detected in an 11-year-old kindred with acute myeloid leukaemia (AML) following intensive treatment of a brain tumour.
We conclude that adenoviral vector-mediated delivery of apoptosis-related genes other than p53 is a potentially useful gene therapy approach toward the treatment of human brain tumors.
Mutations in, and aberrant expression of, the p53 tumor suppressor gene were assessed in 17 cell lines derived from human malignant brain tumors (glioblastoma multiforme).
Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.
However, there is one example of germ-line mutation of p53 gene (the deletion of the codon 236) that is associated with a familiar brain tumor syndrome.
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.