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)

Cytogenetic and molecular studies in neuroblastoma suggest the presence of a tumour suppressor gene at the distal chromosome band 1p36. Previously, we hypothesised that a constitutional translocation involving the region 1p36 [t(1;17)(p36;q12-q21)] in a patient with neuroblastoma predisposed him to tumour development. Here we report the molecular delineation of the translocation breakpoints. Somatic cell hybrids containing the derivative chromosomes were used to determine the position of chromosome 1p and 17q DNA probes respective to the breakpoints using fluorescence in situ hybridisation. The 1p breakpoint was localised between the PND and D1S56 loci. The chromosome 17q breakpoint is flanked by NF1 and SCYA7, as proximal and distal marker, respectively. We redefined the translocation as t(1;17)(p36.31-13;q11.2-q12). The identification of flanking markers of the breakpoints is a prerequisite for breakpoint cloning and identification of a putative neuroblastoma suppressor gene.
Eur J Cancer 1995
PMID:Characterisation of the chromosome breakpoints in a patient with a constitutional translocation t(1;17)(p36.31-p36.13;q11.2-q12) and neuroblastoma. 757 58

The Deleted in Colorectal Cancer (DCC) gene is a candidate tumour suppressor gene encoding a neural cell adhesion molecule-like transmembrane protein. Over the last year, data supporting DCC inactivation in multiple tumour types have continued to accumulate. Functional studies suggest that DCC may participate in signalling pathways that regulate cell proliferation and/or differentiation, two cellular processes that often go awry during tumorigenesis.
Eur J Cancer
PMID:DCC: linking tumour suppressor genes and altered cell surface interactions in cancer? 757 91

Mutant p53 tumour suppressor gene and c-erbB-2 proto-oncogene are involved in human carcinogenesis, and their protein product detection in human malignancies might influence the evolution of many neoplasms. Our aim was to estimate their association with histopathological and clinical parameters of prognostic value in colorectal cancer. An immunohistochemical assay was undertaken in formalin-fixed sections from tissue specimens of 60 colorectal carcinomas. Nuclear p53 expression was detected in 46.6%, while membranic c-erbB-2 positivity was noticed in 35% of the examined cases. P53 positivity rate significantly correlated with poor differentiation (p < 0.001), high mitotic activity (p < 0.0001), tumour stage (p < 0.001) and 5-year overall survival period (p < 0.01). C-erbB-2 positivity incidence significantly correlated with advanced Dukes' stage (p < 0.001) and high mitotic activity (p < 0.05). Significant association between p53 and c-erbB-2 immunostaining was observed (p < 0.05) and p53/c-erbB-2 co-expression was related to poor differentiation (p < 0.001), high mitotic activity (p < 0.001), advanced Dukes' stage (p < 0.001), tumour aneuploidy (p < 0.05) and worse overall survival (p < 0.05). P53 and c-erbB-2 immunohistochemical detection in combination with known prognostic indicators may be a useful future tool in determining colorectal cancer prognosis and subsequently in deciding on optimal postoperative treatments.
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PMID:Prognostic significance of p53 and c-erbB-2 immunohistochemical evaluation in colorectal adenocarcinoma. 757 15

For several human tumour types, allelic loss data suggest that one or more tumour suppressor genes reside telomeric to the p53 gene at chromosome 17p13.1. In the present study we have used a new strategy, involving molecular analysis of a DNA site hypermethylated in tumour DNA, to identify a candidate gene in this region (17p13.3). Our approach has led to identification of HIC-1 (hypermethylated in cancer), a new zinc-finger transcription factor gene which is ubiquitously expressed in normal tissues, but underexpressed in different tumour cells where it is hypermethylated. Multiple characteristics of this gene, including the presence of a p53 binding site in the 5' flanking region, activation of the gene by expression of a wild-type p53 gene and suppression of G418 selectability of cultured brain, breast and colon cancer cells following insertion of the gene, make HIC-1 gene a strong candidate for a tumour suppressor gene in region 17p13.3.
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PMID:p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3. 758 25

Loss of heterozygosity on chromosome 9p21 is one of the most frequent genetic alterations identified in human cancer. The rate of point mutations of p16, a candidate suppressor gene of this area, is low in most primary tumours with allelic loss of 9p21. Monosomic cell lines with structurally unaltered p16 show methylation of the 5' CpG island of p16. This distinct methylation pattern was associated with a complete transcriptional block that was reversible upon treatment with 5-deoxyazacytidine. Moreover, de novo methylation of the 5' CpG island of p16 was also found in approximately 20% of different primary neoplasms, but not in normal tissues, potentially representing a common pathway of tumour suppressor gene inactivation in human cancers.
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PMID:5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. 758 41

Recent investigations revealed that the 9p arm and 17q arm of human chromosomes harbour tumour suppressor genes (TSGs) with an important role in multistage carcinogenesis. At the 9p arm is located the p16 (MTS1) TSG and probably others with an effect on various human tumours such as acute lymphoblastic leukaemia, bladder cancer, gliomas, malignant mesotheliomas, melanomas and non-small cell lung carcinomas. In addition, the 17q arm harbours BRCA1 TSG which is responsible for approximately 80% of the familial breast/ovarian cancer cases. In order to investigate the implication of these performed a loss of heterozygosity (LOH) analysis with 10 polymorphic microsatellite markers (three at the 17q arm surrounding the BRCA1 region and seven at the 9p arm). Fourteen of the 17 (82%) tumours exhibited deletions at 9p. The highest incidence of LOH (6/13, 46%) was found for the marker D9S157 at 9p22. One sample exhibited deletion of all the informative markers tested indicating deletion of the complete 9p arm. No homozygous deletions were found. LOH at the 17q arm near the BRCA1 locus was found in 6 (35%) among 17 specimens. The results of this study indicate that allelic deletions at 9p are frequent in the development of laryngeal tumours. The highest incidence of LOH was found for the marker D9S157 which is near, but distinct from the location of p16 (MTS1) tumour suppressor gene, indicating the presence of multiple tumour suppressor genes within this chromosomal region. In addition, BRCA1 TSG is implicated in the development of laryngeal tumours.
Cancer Lett 1995 Oct 20
PMID:Loss of heterozygosity at 9p and 17q in human laryngeal tumors. 758 72

The retinoblastoma (RB) tumour suppressor gene has been associated not only with retinoblastoma but also with several other tumours like osteosarcoma, small cell lung carcinoma and prostate and breast cancer. We have studied the incidence of RB gene alterations in 96 primary breast tumours using Southern blotting techniques. The outcome has been related with patient and tumour characteristics, oncogene amplifications, p53 mutations and prognosis. RB gene alterations were found to occur more frequently in estrogen receptor (ER)-positive than in ER-negative tumours and less frequently in tumours with oncogene amplification than in tumours without oncogene amplification of HER2/neu, c-myc or 11q13. RB gene alteration was observed in tumours both with and without a p53 gene mutation. Data on 87 patients (mean age, 59.6 years; median follow-up, 108 months) and RB gene alterations revealed a significant association between the frequency of RB gene alterations and node-negative patients (p < 0.01) or smaller (< 2 cm) tumours (p < 0.01), but no relation with age, differentiation grade or (relapse-free) survival. Patients with and without RB gene alterations showed the same relapse-free and overall survival.
Int J Cancer 1995 Apr 21
PMID:Association between RB-1 gene alterations and factors of favourable prognosis in human breast cancer, without effect on survival. 761 56

Allelotypic evaluation of loss of heterozygosity (LOH) has been instrumental in the identification of tumour suppressor genes. Here we report a high incidence of LOH at chromosome 11q23 in non-familial breast cancers with in situ, invasive, and metastatic tumour cells microdissected from archival haematoxylin and eosin (H & E) sections for polymerase chain reaction (PCR)-LOH analysis at polymorphic microsatellite loci. Ninety-four cases of non-familial breast cancer were examined at the D11S29 microsatellite locus on chromosome 11q23. Eighty-three cases (88 per cent) were informative and 35 cases overall (42 per cent) had LOH at this locus, comprising 23 per cent of in situ, 36 per cent of invasive, and 28 per cent of metastatic cancers. The DNA from those cancer cells with LOH was amplified at microsatellite loci D11S554 (11p12-p11.2) and D11S534 (11q13). In 19 of 67 cases overall (28 per cent), LOH occurred solely at 11q23. There was an association between LOH at 11q23 and tumour size > or = 2 cm (P < 0.01) in the overall results and the invasive cancers. The data revealed heterogeneity for LOH at D11S29 in in situ, invasive, and metastatic cells from the same case. In general, however, there was concordance between LOH (or its absence) in in situ and invasive disease. We conclude that the distal part of the long arm of chromosome 11 contains a region involved in breast carcinogenesis and that there is molecular heterogeneity at this chromosomal region in individual breast cancer cells.
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PMID:Mutation at chromosome 11q23 in human non-familial breast cancer: a microdissection microsatellite analysis. 761 53

Mutations of the p53 tumour suppressor gene are common to many human malignancies. Although increased p53 expression has been observed in cutaneous malignant melanoma, mutations of the p53 gene appear to be infrequent. We examined 140 benign and malignant paraffin-embedded melanocytic lesions for p53 protein expression by immunohistochemistry, using the monoclonal anti-p53 antibody DO-7 and a microwave method of antigen retrieval. Fifteen naevi and 25 melanomas were further analysed for p53 mutations within exons 5-8 of the p53 gene. DNA was extracted from paraffin sections and screening for mutations was carried out using PCR-SSCP. We demonstrated p53 protein expression in 33% of naevi (17 out of 51), 35% of primary melanomas (20 out of 58), and 70% of metastatic lesions (15 out of 21). p53 expression in benign lesions was weaker than in malignant lesions in intensity and percentage of cells staining. p53 protein expression in melanomas increased in intensity and percentage of cells staining with tumour progression. In 25% (three out of 12) of metastatic melanomas p53 mutations were detected by PCR-SSCP and increased expression of p53 protein was observed in these tumours. p53 gene mutations were not detected in any benign melanocytic lesions. We demonstrate that antigen retrieval techniques increase p53 immunoreactivity in paraffin embedded melanocytic tissues. p53 protein expression in melanomas increases with depth of tumour invasion. As p53 gene mutations occur infrequently in malignant melanoma, other mechanisms are proposed to influence p53 protein expression in melanocytic lesions.
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PMID:p53 gene mutation and expression in naevi and melanomas. 762 Mar 45

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). The most consistent changes seen are those of allelic loss events, with the majority of tumours examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, seem to be the most frequent regions of loss, suggesting the presence of novel tumour suppressor genes. Deletions of one copy of the RB and TP53 genes are less frequent as are mutations of the TP53 gene, and accumulating evidence suggests the presence of an additional tumour suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation modulated gene expression. The presence of multiple changes in these tumours is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way, which may elucidate critical early events in prostatic carcinogenesis.
Cancer Surv 1995
PMID:Molecular biology of prostate cancer progression. 762 57


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