The results of the study demonstrate that TP53 gene mutations occur in some of endometrioid endometrial cancers in the presence of PTEN gene mutations, suggesting that both these genes participate in the development of these tumors.
Patients who had the allele Pro of the TP53Arg72Pro polymorphism had an increased risk of tumor development (odds ratio, OR = 3.23; confidence interval at 95%, 95%CI = 1.71-6.08; P = 0.003), as did the allele Ser of TP53Pro47Ser polymorphism (OR = 1.28; 95%CI = 0.03-2.10; P = 0.01).
Twenty-four tumours from 15 FCCTX families were analysed for loss of known tumour suppressor gene (TSG) loci (APC, TP53, SMAD4 and DCC), MGMT and MMR genes promoter methylation, and also APC and KRAS somatic mutations.
While p53 has been extensively characterized as a tumor suppressor, it has been more difficult to determine whether p63 and/or p73 play a similar role.
Colorectal tumors with multiple pit patterns exhibited more advanced pit patterns and higher frequencies of KRAS and/or TP53 mutations than tumors with a single pit pattern.
After adjustment for tumor stage, treatment regimen, and the number of mutations, patients with p53 mutations had significantly greater breast-cancer-specific mortality than did patients without p53 mutations (hazard ratio = 2.86; 95% confidence interval: 1.15-7.11).
Significant p53 overexpression was observed in 2 of 38 tumors, and 9 others had faint staining of a few nuclei ( < 1%). p53 overexpression occurred in no informative tumor with allelic loss or mutation.
SGK1-sensitive mechanisms fostering tumour growth include activation of K(+) channels and Ca(2+) channels, Na(+)/H(+) exchanger, amino acid transporters and glucose transporters, upregulation of the nuclear factor NFkappaB and beta-catenin as well as downregulation of the transcription factors Foxo3a/FKHRL1 and p53.
While ATL patients carrying a wild-type p53 enter remission following treatment with AZT, those with a mutated p53 did not respond, and patients' disease relapse was associated with the selection of a tumor clone carrying mutated inactive p53.
Together, these results indicate that RNF2 is an E3 ligase for p53 degradation in selective cells, implicating RNF2 as a therapeutic target to restore tumor suppression through p53 in certain tumor cells.
This analysis suggest that PTEN gene mutations are restricted to high-grade adult gliomas and that this abnormality is independent of the presence or absence of gene amplification or p53 gene mutation in these tumors.
In conclusion, the in vitro and in vivo data demonstrate, for the first time, a novel mechanism by which the tumor suppressor functions of TFF1 involve activation of p53 through down-regulation of miR-504.
Loss of heterozygosity analyses were done using five microsatellite polymorphic markers that represent putative tumor suppressor genes on chromosome 3p14 (D3S1300), 7q31 (D7S522), 8p22 (D8S261), 9p21 (D9S171), and 17p13 (TP53).
Significant correlations of number, height, angle, fusion and Paneth cell metaplasia of crypts, as well as thickness of the muscularis mucosae, were revealed with disease duration, as confirmed by three-dimensional reconstructed image analysis. p53 and p21(WAF1)-positive cells increased with disease duration and were significantly more frequent in cases with neoplasia, suggesting more DNA damage.
Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively.
No somatic TP53 mutations were found, but tumor-associated HPV 16 E6 sequences were retrieved from the 12- and 25-year-old, while both HPV 16 and HPV 18 E6 sequences were found in the tumor of the 15-year-old and in its associated metastasis.