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)

Adenocarcinoma arising in Barrett's oesophagus is often preceded by mucosal dysplasia, but little is currently known about the aetiology or natural history of this dysplasia/carcinoma sequence. To investigate the participation of the tumour suppressor gene p53 in this sequence, an immunohistochemical analysis of p53 protein overexpression, which is known to closely correlate with point mutation of the p53 gene, was conducted in 30 patients with Barrett's adenocarcinoma. Adjacent Barrett's mucosa was dysplastic in 21 (70%) patients. Sixteen (53%) tumours overexpressed p53, 10 of which had adjacent dysplastic Barrett's mucosa. In all 10 patients, this dysplastic mucosa also overexpressed p53, predominantly in areas of high grade compared with low grade dysplasia. In contrast, none of the dysplastic mucosa adjacent to 11 tumours lacking p53 overexpression showed detectable values of p53. These results suggest that p53 dysfunction may participate in the progression from dysplasia to carcinoma in some patients with Barrett's oesophagus.
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PMID:Adenocarcinoma arising in Barrett's oesophagus: evidence for the participation of p53 dysfunction in the dysplasia/carcinoma sequence. 802 Aug 1

The detection in tumors of genomic regions with a high frequency of loss of heterozygosity has led to the localization and subsequent cloning of a number of tumour suppressor genes. To identify such regions involved in the development of squamous carcinoma of the head and neck we have analyzed 28 paired normal and tumor DNA samples. Using the polymerase chain reaction to amplify 50 simple sequence repeats or microsatellite markers we have studied all 22 q limbs and 17 of the p limbs in 21 patients. In informative cases we observed a high incidence of loss of heterozygosity at five specific chromosomal regions: 3p (44%); 5q (43%); 9q (35%); 11q (45%); and 17p (31%). In addition, further analysis of tumors showing loss of heterozygosity at 5q suggests that a gene at or near the APC locus is involved in squamous carcinoma of the head and neck.
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PMID:An allelotype of squamous carcinoma of the head and neck using microsatellite markers. 813 68

The neurofibromatosis 2 gene (NF2) has recently been isolated and predicted to encode a novel protein related to the moesin-ezrin-radixin family of cytoskeleton-associated proteins. Here we describe a novel isoform of the NF2 transcript that shows differential tissue expression and encodes a modified C terminus of the predicted protein. Mutations affecting both isoforms of the NF2 transcript were detected in multiple tumour types including melanoma and breast carcinoma. These findings provide evidence that alterations in the NF2 transcript occur not only in the hereditary brain neoplasms typically associated with NF2, but also as somatic mutations in their sporadic counterparts and in seemingly unrelated tumour types. The NF2 gene may thus constitute a tumour suppressor gene of more general importance in tumorigenesis.
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PMID:Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. 816 73

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

In this study we have analysed 38 squamous cell carcinomas (SCC) two basal cell carcinomas (BCC), a malignant salivary gland carcinoma, a neurosarcoma and a Warthins carcinoma, all isolated from patients with head and neck cancers. These tumour types have been examined by PCR for loss of heterozygosity (LOH) on both arms of chromosome 17 using nine polymorphic microsatellite markers. LOH on 17p in SCCHN was found to be 50% (19/38), and often involved TP53 (42%) but more frequently involved the CHRNB1 locus (56%). Twelve tumours showed loss of heterozygosity on 17q (34%) and ten of these also had loss on 17p. Four SCCHN tumours lost an entire copy of chromosome 17. It was of particular note that 77% (10/13) of the SCCHN at the hypopharyngeal site had LOH at CHRNB1. We propose from our data that the 17p12-p11 region contains a novel predisposing gene for hypopharyngeal SCCHN that may function as a tumour suppressor gene.
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PMID:Loss of heterozygosity studies on chromosome 17 in head and neck cancer using microsatellite markers. 820 54

Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary nonpolyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4-15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas.
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PMID:Genomic instability occurs in colorectal carcinomas but not in adenomas. 825 87

Cervical cancer is similar to other human cancers in that it develops through a multistep process. However, infection with oncogenic human papillomaviruses (HPVs) is believed to be essential for the initiation of this disease. Although HPV may play a central role in the early stages of neoplasia, the accumulation of mutations in an assortment of genes precedes the development of malignant cervical carcinoma. The mechanisms by which abnormalities accumulate are various, but it is possible that viral proteins are involved. In particular, the viral E6 oncoprotein has been shown to interact with the cellular tumour suppressor protein p53, which is involved in DNA damage repair pathways. Hence, E6 may contribute to the genomic instability through this interaction with p53. We have tested this hypothesis by monitoring the effects of E6 upon DNA damage induced p53 transcriptional activity. This study shows that HPV-18 E6 inhibits p53 transcriptional activity following genotoxic stress with UV radiation. No effect was observed when a mutant E6 unable to direct the degradation of p53 was included in this assay. These results suggest that continued E6 expression may contribute to the accumulation of DNA damage associated with the progression of cervical cancer.
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PMID:DNA damage induced p53 mediated transcription is inhibited by human papillomavirus type 18 E6. 829 Feb 74

Tissue markers of potential malignancy have been sought for many years. Cell surface markers, particularly blood group and histocompatibility antigens, have shown great promise and several squamous carcinoma antigens have been identified--but not fully studied in potentially malignant lesions. Growth factors and receptors also need further study. Cytoplasmic markers of potential malignancy have been examined and, of these, keratins, filaggrin, and some carcinoma antigens show most promise. Nuclear analyses have promise but are time-consuming and expensive. Image cytometric analyses appear to be sensitive and predictive: oncogene and tumour suppressor analyses remain to be fully evaluated. New investigative techniques at the cellular and molecular level show increasing promise at defining potentially malignant oral epithelial lesions but more prospective studies are required.
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PMID:Tissue markers of potentially malignant human oral epithelial lesions. 835 23

There is now a considerable body of evidence that links HPV infection with anogenital squamous carcinoma, particularly for specific 'high risk' HPV types (HPV16 and 18) and invasive carcinoma of the cervix. Recent advances in the molecular study of these viruses have elucidated some potential mechanisms by which they may contribute to the development of these diseases. In this review we concentrate on the interactions of 2 of the HPV encoded proteins, E6 and E7, with cellular tumour suppressor gene products. We provide a model of how these interactions may be important in tumourigenesis and draw together current knowledge of this exciting and rapidly evolving field.
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PMID:Human papillomaviruses, tumour suppressor genes and cervical cancer. 839 53

Mutations in the p53 tumour suppressor gene are amongst the most frequent genetic abnormalities acquired in tumours. Recent studies in vitro suggest that mutant p53 destabilises the genome and facilitates development of aneuploidy. Here, in a study of 83 colorectal carcinomas, we demonstrate that alterations in p53 (detected by immunocytochemical stabilisation) precede and apparently facilitate divergence of aneuploid sub-clones. Aneuploidy in these tumours (but not those with normal p53) is predominantly in the subtetraploid range, suggesting that endoreduplication is important in its origin. This association with a specific phase of carcinoma progression is not shared by other commonly acquired genetic abnormalities in these tumours. These observations highlight the critical role of p53 in the regulation of abnormal chromosome replication and afford an explanation for the association between p53 abnormalities, aneuploidy and biological aggression in cancer.
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PMID:Stabilised p53 facilitates aneuploid clonal divergence in colorectal cancer. 847 57


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