Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.
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PMID:Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance. 778 34

Forty-eight primary oral squamous cell carcinomas (SCC) were screened for allelic imbalance (AI) at 3p24-26, 3p21, 3p13, 8p21-23, 9p21, 9q22 and within the Rb, p53 and DCC tumour suppressor genes. AI was detected at all TNM stages with stage 4 tumours showing significantly more aberrations than stage 1-3. A factional allelic loss (FAL) score was calculated for all tumours and a high score was associated with development of local recurrence (P = 0.033) and reduced survival (P = 0.0006). AI at one or more loci within the 3p24-26, 3p21, 3p13 and 9p21 regions or within the THRB and DCC genes was associated with reduced survival. The hazard ratios for survival analysis revealed that patients with AI at 3p24-26, 3p13 and 9p21 have an approximately 25 times increase in their mortality rate relative to a patient retaining heterozygosity at these loci. AI at specific pairs of loci, D3S686 and D9S171 and involving at least two of D3S1296, DCC and D9S43, was a better predictor of prognosis than the FAL score or TNM stage. These data suggest that it will be possible to develop a molecular staging system which will be a better predict of outcome than conventional clinicopathological features as the molecular events represent fundamental biological characteristics of each tumour.
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PMID:The prognostic significance of allelic imbalance at key chromosomal loci in oral cancer. 1020 99

Development of databases, summarising the genetic events associated with oral squamous cell carcinoma (SCC), should increase our understanding of the molecular basis of these lesions. Additionally, databases will help establish whether different cancer subtypes show different growth characteristics, because the multistage carcinogenic process is different in the various tumour subtypes. This new knowledge may also provide new prognostic information, as these aberrations represent fundamental biological characteristics of each tumour. To assess the value of incorporating the results from loss of heterozygosity (LOH) analysis into patient-specific mutation databases, we have carried out microsatellite analysis with 52 polymorphic markers at 13 key chromosomal regions implicated in the pathogenesis of head and neck cancers. Altered expression of the Rb, p53 and DCC tumour suppressor genes has also been studied by immunohistology. Our results shed light on the different pathways that lead to cancer and reveal that a variety of different patterns of allelic imbalance (AI) were detected at all TNM stages, reflecting the different clinical behaviour that tumours classified as being of the same TNM stage may exhibit. Summarising the level of genetic damage as a fractional allelic loss (FAL) score and the presence of AI at 3p22-26, 3p14.3-12.1 and 9p21 was found to be a better predictor of outcome than the TNM system. This finding suggests that molecular data can be incorporated into conventional staging systems to provide more accurate prognostic information for this group of patients.
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PMID:Patient-specific mutation databases for oral cancer. 1037 48

The prognostic value of disseminated tumour cells derived from 353 breast cancer patients was evaluated. Disseminated tumour cells were purified from blood using a newly established method and nucleic acids were subsequently isolated. We investigated genomic imbalances (GI) such as mutation, amplification and loss of heterozygosity of 13 tumour suppressor genes and 2 proto-oncogenes using DNA from isolated minimal residual cancer cells. Significant correlations were found between genomic alterations of the DCC - and c-erbB-2 genes in disseminated breast cancer cells and actuarial relapse-free survival. Furthermore, increasing numbers of genomic imbalances measured in disseminated tumour cells were significantly associated with worse prognosis of recurrent disease. Logistic regression and Cox multivariate analysis led to the identification of genomic imbalances as an independent prognostic factor. Determination of disseminated tumour cells by genotyping of oncogenes and tumour suppressor genes seems not only to be a useful adjunct in follow up of carcinoma patients but provides also valuable additional individualized prognostic and predictive information in breast cancer patients beyond the TNM system.
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PMID:Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients. 1110 64

The WISPs (Wnt-inducted secreted proteins, WISP-1, WISP-2 and WISP-3) are part of the CCN family. These molecules are known to play a diverse role in cells but their role in cancer cells remains controversial. We analysed the expression of the three WISP molecules at the mRNA and protein levels in a cohort of 94 human colorectal tumours and 80 normal colorectal tissues and correlated the results with the pathological features and clinical outcome of the patients. WISP-1 transcripts were found at higher levels in the tumour samples than in the normal tissue (p=0.0015); higher in patients with Dukes stage B and C compared to Dukes A (p=0.017 and p=0.024, respectively); higher in patients with moderately and poorly differentiated cancers compared to the well differentiated cancers (p=0.020 and p=0.076, respectively and p=0.0035 when combined); higher in node positive tumours compared with the node negative (p=0.11) and in the patients with higher TNM staging (TNM 2, 3 and 4 compared to TNM 1 p=0.037). WISP-2 showed the opposite pattern with lower levels of expression in cancer cells compared to normal (p=0.082). Although no significant differences were found within the cancer group when indices of a more aggressive tumour were compared to the normal tissue a significant reduction in expression was found (Dukes C p=0.044, poorly differentiated p=0.019, TNM 3 p=0.020 and node positive disease p=0.048). WISP-3 transcript levels showed no significant differences between groups. WISPs may play important but contrasting roles in colorectal cancer with WISP-1 appearing to act as a factor stimulating aggressiveness, WISP-2 as a tumour suppressor and WISP-3 having no definable beneficial or detrimental role.
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PMID:Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications. 2037 86

The methylation of CpG islands in the promoters is associated with loss of protein via repression of gene transcription. Several studies have demonstrated that tumour suppressor and DNA repair genes are often aberrantly hypermethylated in colorectal cancer. The present study was conducted to examine whether the methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was associated with clinical features and patients' survival in CRC (colorectal carcinoma). Aberrant methylation of p16INK4a and hMLH1 promoters was found in 47.2 and 53.4% of tumours respectively. For adjacent non-tumoral mucosa, p16INK4a was fully unmethylated in 30% of the cases, whereas hMLH1 was predominantly unmethylated (76%). Methylation of p16INK4a correlated with gender and tumour size (P=0.005 and 0.035 respectively), whereas those of hMLH1 significantly correlated with overall survival (P log rank=0.007). Concomitant methylation of p16INK4a and hMLH1 was associated with TNM (tumour, lymph node and metastases) stage and tumour size (P=0.024 and 0.021 respectively). Our data show that loss of hMLH1 expression through aberrant methylation could be used as a marker of poor prognosis in CRC.
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PMID:Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic colorectal adenocarcinoma. 2081 11

Loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour suppressor genes. We have undertaken extensive allelotyping of 45 specimens of non-small cell lung cancer (NSCLC) using 92 polymorphic microsatellite markers on 39 chromosome arms. The most frequent allelic imbalances were found on chromosome arms 3p, 9p and 17p. Significant allelic imbalance was found on other chromosome arms including, 5q (21%), 8p (19%), 13q (24%) and 17q (18%). The LOH data on 3p was subdivided into the four chromosomal regions considered to contain putative tumour suppressor genes 3p25-p24 (10%), 3p21 (10%), 3p14 (25%) and 3p13-p12 (22%). The frequency of loss in the different regions on 9p were: 9pter-p23 (31%), 9p23-p22 (45%) and 9p21-cent (30%). LOH on 17p was separated into three regions: 17pter-p13 (9%), 17p13 (33%) and 17p13-cent (22%). No correlation was found between LOH on any of the chromosomal arms and any of the clinicopathological parameters such as pathology, level of differentiation, TNM staging or alcohol intake. Only one significant association was found between LOH and tumour types. A significant difference was found between LOH on 17q in adenocarcinomas and squamous cell carcinomas (p=0.037). The fractional allele loss (FAL) values for this group of 45 NSCLC gave a median value of 0.9 (range 0-0.45). No correlation was found between FAL and nodes at pathology (p>0.05) and between FAL and tumour grade (p>0.05). No correlation was found between p53 or ras mutations in these NSCLC specimens and their FAL values. Accumulated genetic damage, as provided by this allelotype analysis, provides a useful molecular parameter by which to assess NSCLC and may, in time, assist in the determination of the clinical behaviour and clinical outcome of these tumours.
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PMID:Allelotype of non-small cell lung cancer. 2154 47

Cytogenetic studies in squamous cell carcinoma of the head and neck (SCCHN) have identified a clustering of breakpoints in a number of chromosomes, including chromosome 3. We have undertaken a loss of heterozygosity analysis (LOH) of 36 SCCHN and six solid tumours which were not squamous cell, and their respective normal specimens, using a bank of microsatellite markers, with the aim of identifying specific sites of frequent loss on chromosome 3. The analysis was undertaken with 12 microsatellite markers, 10 of which are on the p arm of chromosome 3. Allelic loss greater than 10% was seen at four sites; D3S1269 (13%), D3S1079 (23%), D3S659 (23%) and D3S1293 (31%). None of this series of tumours showed loss of the whole chromosome, however 47% of the tumours analysed had LOH at one or more loci. The highest incidence of LOH was found at D3S1293 in the 3p24-p25 region. The second highest region with LOH was found at D3S1079 and D3S659 at 3p13. The remaining markers telomeric and centromeric to these two regions were found to have a LOH of less than 10%. Furthermore, we found a strong association between loss of one marker on chromosome 3 in these SCCHN and poor clinical prognostic indicators; such as site, pathological differentiation, positive nodes at pathology (p<0.05) and TNM status (p<0.05). This study has identified two regions in SCCHN that are most likely to be important in the development of squamous cell carcinoma of the head and neck at 3p24-p25 and 3p13 and may indicate sites of novel tumour suppressor genes in this disease.
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PMID:Allele loss on chromosome-3 in squamous-cell carcinoma of the head and neck correlates with poor clinical prognostic indicators. 2156 56

Breast cancer is the most common cancer in women worldwide, representing 28.2% of all female malignancies. In addition to genetic changes, epigenetic events, as aberrant DNA methylation and histone modification, are responsible for cancer development. Many tumour suppressor genes are inactivated by DNA hypermethylation, which could be utilized for identification of new epigenetic biomarkers. To investigate the relation between DNA methylation level and breast cancer progression, we analysed DNA methylation in RASSF1A and CDH1 promoters using quantitative multiplex methylation-specific PCR in paraffin-embedded tumour tissues and blood samples from 92 breast cancer patients and 50 controls, respectively. The associations between RASSF1A and CDH1 methylation levels and clinico-pathological parameters were tested by Kruskal-Wallis and van der Waerden ANOVA tests. Out of 92 breast cancer patients, 76 (82.6%) manifested various levels of RASSF1A (range from 1.20 to 92.63%) and 20 (21.7%) of CDH1 (range from 1.20 to 79.62%) methylation. However, no methylation was found in 50 controls. Increasing trends in RASSF1A methylation were observed in tumour size, lymph node status and TNM stage, but only CDH1 methylation levels showed statistically significant differences between the patient subgroups in lymph node status and IHC subtype. Overall, stable relatively high RASSF1A methylation could be utilised as universal tumour marker and the less frequent but highly methylated CDH1 promoter can serve for identification of potentially metastasising tumours.
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PMID:RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer. 2229 48

Five years survival of lung cancer is 16%, significantly lower than in prostate (99.9%), breast (88.5%) and colon (64.1%) carcinomas. When diagnosed in the surgical stage it increases to 50% but this group only comprises 14-16% of the cases. DNA methylation has emerged as a potential cancer-specific biomarker. Hypermethylation of CpG islands located in the promoter regions of tumour suppressor genes is now firmly established as an important mechanism for gene inactivation. This retrospective study included 40 squamous cell carcinomas and 40 adenocarcinomas in various surgical TNM stages to define methylation profile and possible silencing of DNA repair genes - MLH1 and MSH2 - using Methylation-Specific PCR and protein expression by immunohistochemistry in tumoural tissue, preneoplastic lesions and respiratory epithelium with normal histological features. The protein expression of MLH1 and MSH2 genes, in the available preneoplastic lesions and in normal cylindrical respiratory epithelium appeared reduced. The frequency of promoter hypermethylation found on these DNA repair genes was elevated, with a higher prevalence of methylation of MLH1 gene in 72% of squamous cell carcinoma. The differences are not so obvious for MSH2 promoter hypermethylation. No correlation was found among the status of methylation, the protein expression and the clinicopathological characteristics. With a larger study, a better characterization of the hypermethylation status of neoplastic and preneoplastic lesions in small biopsies would be achieved, inherent to tumour histology, heterogeneity and preservation, and finally differences in the study population to elucidate other possible mechanisms of altered expression of the hMLH1 and hMSH.
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PMID:Promoter hypermethylation of DNA repair genes MLH1 and MSH2 in adenocarcinomas and squamous cell carcinomas of the lung. 2436 Mar 95


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