A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has been negatively associated with onset and outcome of disease in solid tumors.
An identical p53 mutation was invariably present in all samples from primary and metastatic colorectal tumor biopsies within the same patient. p53 mutations were detected in peripheral blood from 8 of these 19 patients with p53-mutated solid tumors.
Appreciation of the function of the tumor suppressor gene p53 has given new insight into regulation of the cell cycle, and the gene appears to play an important role in many solid tumors.
Base substitutions at A:T pairs constitute an important fraction of ESC p53 mutations, in contrast to mutation patterns in most other types of solid tumors.
For assessment of p53 and PCNA positivity, the number of positively stained cells with brown-stained nuclei was counted in 1000 cells from each sample. p53 and PCNA expression in the solid neoplasm subtype were significantly higher when compared to cystic neoplasm and simple cyst (P < 0.05).
In solid tumors, p53 antibodies are found in 30% of the patients with p53 mutations, and their analysis is an interesting method for the detection of p53 mutations.
In dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible.
In NF1 syndrome, loss of p53 function is a common event in solid tumors, but uncommon in JMML, suggesting that the p53 pathway may be modified by other events in this hematopoietic disorder.
In normal tissue and solid tumors presumably other functions have more impact on the cellular response. p53 controls cell-cycle progression after irradiation and also DNA-repair, namely homologous and non-homologous recombination.
In patients with detected hotspot TP53 mutant advanced solid tumors (n = 11), the treatment led to a 45% rate of SD ≥6 months/PR (1 PR and 3 SD ≥6 months), median PFS of 3.5 months, and median OS of 12.7 months, compared favorably with the results for patients with undetected hotspot TP53 mutations (n = 25): 16% (1 PR and 3 SD ≥6 months, P = 0.096), 2.0 months (P = 0.042), and 7.4 months (P = 0.1), respectively.
In pediatric solid tumors, such as neuroblastoma (NB), it has been reported that the frequency of TP53 gene alterations is lower than that in adult tumors, suggesting that other tumor suppressor genes may play more important roles in the development of pediatric solid tumors.
In this study we show that p53 is required for the downregulation of FoxM1, an essential transcription factor that regulates many G2/M-specific genes and is overexpressed in a multitude of solid tumors.
In this study, we investigated GSTM1, GSTT1 and p53 codon 72 polymorphisms in a variety of human tumor cell lines originating from different organs to clarify tissue-specific polymorphic frequency of these genes in human solid tumors.
In view of the difficulty in controlling mutated p53 status tumors and intratumor Q cells, combination treatment with MTH and/or TPZ as a cooperative modality in cancer therapy is considered to have potential for controlling solid tumors as a whole.
It binds to and inhibits key proteins like p53 and the RB protein, and MDM2 amplification as well as protein overexpression without amplification is seen in many solid tumors.
Mutations of the p53 gene on exons 5 through 8 were examined in 82 childhood malignant solid tumors by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method, and the nature of these mutations was confirmed by direct sequencing.