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

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.
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PMID:Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa. 782 4

Intragenic restriction site polymorphisms in amino acid residue 72 in exon 4 and a Mspl polymorphism in intron 6 of the p53 tumour suppressor gene can both serve as polymorphic markers. Probe YNZ22 (D17S5) is a highly polymorphic, variable number of tandem repeat (VNTR) marker which maps to chromosome 17p13.1 where the p53 gene is located. Locus specific amplification by polymerase chain reaction (PCR) technique and subsequent non-isotopic single-strand conformation polymorphism analysis of the PCR fragments was used for the detection of loss heterozygosity (LOH) of 17p including the p53 gene locus. In combination with a PCR-based method for the analysis of the VNTR locus D17S5 using unique sequences flanking the polymorphic region of YNZ22 we investigated tumour DNA and corresponding constitutional DNA from 69 patients, including 39 patients with gastric cancer, 21 patients with osteosarcomas and 9 patients with Ewing's sarcomas. Using all three methods, 49/69 (71%) patients were informative for LOH, which revealed allelic loss in 5/39 (12.8%) gastric cancers, 1/9 (11.1%) Ewing's sarcoma, and 4/20 (20%) osteosarcomas.
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PMID:Rapid detection of loss of heterozygosity of chromosome 17p by polymerase chain reaction-based variable number of tandem repeat analysis and detection of single-strand conformation polymorphism of intragenic p53 polymorphisms. 791 80

Gastric cancer is more than twice as common in Hispanics as in Anglos in Texas, while colorectal cancer is almost twice as common in Anglos as Hispanics. To test the hypothesis that mutations in the p53 tumour suppressor gene are involved in these differences, we examined 131 gastric and 138 colorectal cancers from Hispanic and Anglo patients from South Texas and Mexico using immunohistochemistry (IHC) as a screening assay for p53 mutations. The fraction of p53 positive cases was not significantly different in gastric cancers from Hispanics compared to Anglos (43% versus 61%, respectively, p = 0.13) or in colorectal cancer (57% versus 58%, respectively, p = 1.0), suggesting that p53 mutations are not involved in causing the different incidences of these cancers in these populations. In addition, the types of p53 mutations arising in gastric tumours from Hispanic patients were consistent with those reported in gastric tumours in other populations. Sequencing of mutations in five gastric cancers revealed two G:C to A:T transitions, two A:T to G:C transitions and one complex deletion. In contrast with findings in studies in other tumour types, neither stage nor survival was associated with p53 positive staining by IHC in either gastric or colorectal tumours in this study. Positive p53 immunostaining was associated with the diffuse histological subtype in gastric carcinoma (p = 0.05) and high histological grade in colorectal carcinoma (p = 0.04).
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PMID:p53 mutations in gastric and colorectal cancers in Texas Hispanics versus Anglos. 818 Jul 81

Abnormalities affecting tumour suppressor genes on chromosome 5q21 are increasingly recognised as important in the pathogenesis of a variety of human cancers, particularly of the gastrointestinal tract. We have examined a series of gastric and pancreatic cancers from European patients for loss of heterozygosity (LOH) of markers within and around the APC and MCC genes on chromosome 5q21 using restriction fragment length polymorphism and polymerase chain reaction techniques. We find that LOH of the APC and MCC genes is particularly frequent in gastric cancers of diffuse type, but very infrequent in pancreatic cancers. We have also used single-strand conformational polymorphism to screen for abnormalities of the sequence of the APC and MCC genes in a panel of pancreatic cancer cell lines. Our results suggest that there are distinct differences in the molecular pathogenesis of gastric and pancreatic cancer and that abnormalities of APC and MCC may be involved particularly in the diffuse type of gastric cancer.
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PMID:Abnormalities affecting the APC and MCC tumour suppressor gene loci on chromosome 5q occur frequently in gastric cancer but not in pancreatic cancer. 840 87

Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki-67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur.
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PMID:Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. 843 9

Mutation of the p53 tumour suppressor gene often leads to the accumulation of mutant p53 protein in tumour cells. Many cancer patients develop antibodies that recognize the overexpressed p53 protein. The presence of these antibodies is, in some tumour types, associated with poor prognosis. Gastric cancer is a highly prevalent disease associated with a high rate of mortality, there is a need for improved clinical and biological markers for disease behaviour. To investigate the clinical relevance of serum anti-p53 antibodies in patients with gastric adenocarcinoma, we have examined the sera of 501 gastric cancer patients for the presence of serum antibodies against the p53 protein. By immunoblotting analysis using a cell lysate containing overexpressed p53 protein as well as affinity-purified recombinant p53 protein as antigens, we have detected anti-p53 antibodies in 11.2% (61 of 501) of gastric cancer patients, but in none of 46 cancer-free individuals. The presence of anti-p53 antibodies was tightly associated with tumours of higher nuclear grade and lymph node metastasis, and a negative association was found between the presence of anti-p53 antibodies and survival. These results suggest that a preoperative test of serum anti-p53 antibodies in gastric cancer patients can be useful to identify subset of patients who may need gastrectomy with lymph node dissection and post-operative adjuvant therapy.
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PMID:Serum anti-p53 antibodies in gastric adenocarcinoma patients are associated with poor prognosis, lymph node metastasis and poorly differentiated nuclear grade. 1040 57

We have analysed the loss of heterozygosity (LOH) on chromosome bands 16q22-q24 in 24 primary gastric cancer tissues and found three regions of frequent allelic loss (16q22, 16q24.1-q24.3 and 16q24.3). The region for the most frequent allelic loss (63%) was in 16q24.1-q24.3. LOH of this region had no relationship with histological subtype, but a significant association between LOH and microscopic lymphangial invasion was observed. Although not significant, vascular and gastric wall invasions are also associated with LOH. The region includes the locus for the H-cadherin gene. Therefore we examined the genetic and epigenetic alterations of this gene. Markedly reduced expression was observed in gastric cancer cell lines compared with that of normal gastric mucosa. However, no mutation was found in this gene in any of the gastric cancer tissues or the gastric cancer cell lines. Furthermore, we analysed the methylation status of the 5'-flanking region of the gene, but no significant association was found. We suggest that some other tumour suppressor gene(s) in 16q24.1-q24.3 may be responsible for gastric carcinogenesis.
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PMID:Chromosome band 16q24 is frequently deleted in human gastric cancer. 1040 66

The FHIT (fragile histidine triad) gene has been recently identified and cloned at chromosome 3p14.2 including FRA3B, the most common fragile site in the human genome. FHIT is suggested to be a candidate tumour suppressor gene in gastrointestinal tract tumours. To elucidate the role of the FHIT gene in gastric cancer, a total of 133 curatively R0-resected gastric carcinomas were investigated for loss of heterozygosity (LOH) at 3p14.2, using four polymorphic microsatellite loci (D3S1300, D3S1313, D3S1481, and D3S1234). LOH of the FHIT gene affecting at least one of the investigated loci was observed in 20 of 123 informative tumours (16.3 per cent). The presence of LOH was correlated neither with major prognostic factors such as pT category, pN category or vascular invasion, nor with histological type or grade of differentiation of the tumours. In addition, there were no differences in the prognosis between patients with gastric carcinomas showing LOH at the FHIT gene and patients with tumours lacking LOH at the FHIT gene. These findings suggest that LOH of the FHIT gene represents an event in the tumourigenesis of only a small subset of gastric carcinomas and does not correlate with tumour progression or prognosis.
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PMID:FHIT gene in gastric cancer: association with tumour progression and prognosis. 1044 Jul 47

p53 tumour suppressor gene mutations were analysed in gastric cancer in relation to food habits and social class in 56 patients from a high risk region of Italy. Exons 5-8 were analysed with DGGE method on amplified DNA from formalin-fixed paraffin-embedded samples. All p53 mutations were observed in patients belonging to low social class and the majority of mutations were found in intestinal type cancers. A positive association was also found with low raw vegetables, fresh, dried and preserved fruits, and ascorbic acid intake. Moreover, specific types of mutations were significantly associated with particular factors, thus suggesting the presence of specific molecular etiologic process in stomach carcinogenesis.
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PMID:Relation between food habits and p53 mutational spectrum in gastric cancer patients. 1085 29

Four cases of late onset clear cell renal cell carcinoma (RCC), a case of gastric cancer, and a case of exocrine pancreatic cancer were identified in a Japanese family. In order to elucidate the underlying mechanism for tumorigenesis in this family, extensive genetic studies were performed including routine and spectral karyotyping (SKY), fluorescence in situ hybridisation (FISH), comparative genomic hybridisation (CGH), loss of heterozygosity studies (LOH), and VHL mutation analysis. A germline translocation t(1;3)(q32-q41;q13-q21) was identified by karyotyping in five members of the family including all three RCC cases tested. The translocation was refined to t(1;3)(q32;q13.3) by FISH analysis using locus specific genomic clones, and the two breakpoints were mapped to a 5 cM region in 3q13.3 and a 3.6 cM region in 1q32. Both CGH and allelotyping using microsatellite markers showed loss of the derivative chromosome 3 carrying a 1q segment in the three familial RCCs analysed. Additional chromosomal imbalances were identified by CGH, including amplifications of chromosomes 5 and 7 and loss of 8p and 9. No germline VHL mutation was found but two different somatic mutations, a splice (IVS1-2A>C) and a frameshift (726delG), were identified in two RCCs from the same patient confirming their distinct origin. Taken together, these results firmly support a three step model for tumorigenesis in this family. A constitutional translocation t(1q;3q) increased the susceptibility to loss of the derivative chromosome 3 which is then followed by somatic mutations of the RCC related tumour suppressor gene VHL located in the remaining copy of chromosome 3.
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PMID:Association of a novel constitutional translocation t(1q;3q) with familial renal cell carcinoma. 1123 83


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