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)

Using restriction fragment length polymorphism (RFLP) analysis, we demonstrated in 4 of 20 patients with astrocytomas loss of heterozygosity on the short arm of chromosome 17 (17p), in the telomeric segment distal to DNA marker pEW301 (locus D17S58). The loss of heterozygosity may uncover a mutation in a tumour suppressor gene and thus lead to or permit tumour formation. The p53 tumour suppressor gene, which is localized at 17p13, is a likely candidate for the tumour suppressor gene involved. Of the 4 patients with loss of heterozygosity on 17p, one patient had a grade I astrocytoma, another patient had a grade II astrocytoma and 2 patients had glioblastoma multiforme. Since the loss of heterozygosity on 17p was detected in low-grade as well as in high-grade astrocytomas, it is possible that p53 suppressor gene loss may be an early genetic event in the multistep process of astrocytoma formation.
 ...
PMID:Loss of heterozygosity on the short arm of chromosome 17 in human astrocytomas. 135 Dec 57

The DNA of paired tumour and blood leucocyte samples from a large series of breast cancer patients was analysed to map regions of loss of heterozygosity on chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed, and a third of informative tumours had also lost an allele at the long arm locus THH59. On the short arm two distinct regions of loss of heterozygosity were identified, in bands p13-3 and p13-1. The latter probably involves the structural gene p53, which has been implicated as an oncogene or as a tumour suppressor in various human cancers. 17p 13-3, however, showed a significantly higher frequency of loss of heterozygosity, and there was no correlation between allele losses at the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated with overexpression of p53 mRNA, suggesting the existence of a gene some 20 megabases telomeric of p53 that regulates its expression. Lesions of this regulatory gene seem to be involved in the majority of breast cancers.
 ...
PMID:Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. 197 43

Chronic lymphocytic leukaemia (CLL) is a disease characterised by several immune defects such as frequent autoimmune complications and functional T-cell defects, which lead to an increased risk of infections (mostly bacterial) and other tumours. Clonal chromosome abnormalities are identified in half of the patients, and trisomy 12, the most common aberration, is present in about one-third of patients with clonal changes. The commonest structural abnormalities involve chromosome 13 at band q14, the site of the retinoblastoma tumour suppressor gene. A gene located telomeric to the Rb1 gene, identified by the D13S25 probe, might be a better candidate for a pathophysiologically relevant gene in CLL, since repeated reports have identified homozygous deletions of this site. The purine analogues fludarabine and cladribine (2-chloro-2'-deoxyadenosine) and the adenosine deaminase inhibitor deoxycoformycin all have therapeutic effects in a range of lymphoproliferative disorders. Prolonged immunosuppression with low CD4 cell counts frequently occurs and, subsequently, opportunistic infections may be seen. This has to be taken into consideration when treating patients with any of these potent drugs.
 ...
PMID:Immunological and genetic abnormalities in chronic lymphocytic leukaemia. Impact of the purine analogues. 752 86

Inactivation of the tumour suppressor gene lethal(2) giant larvae (D-lgl) of Drosophila leads to malignant transformation of the presumptive adult optic centers in the larval brain and tumours of the imaginal discs. These malignancies result from the disorganization of a cytoskeletal network in which the D-LGL protein participates. Here we describe the isolation of a cDNA encoding the human homologue to the D-lgl gene designated as hugl. The hugl cDNA detects a locus spanning at least 25 kilobases (kb) in human chromosome band 17p11.2-12, which is centromeric to the p53 gene and recognizes a 4.5 kb RNA transcript. The hugl gene is expressed in brain, kidney and muscle but is barely seen in heart and placenta. Sequence analysis of the hugl cDNA demonstrates a long open reading frame, which has the potential to encode a protein of 1057 amino acids with a predicted molecular weight of 115 kDaltons (kD). To further substantiate and identify the HUGL protein, we have prepared polyclonal rabbit antibodies against synthetic peptides corresponding to the amino and carboxyl termini of the conceptual translation product of the hugl gene. The affinity-purified anti-HUGL antibodies recognize a single protein with an apparent molecular weight of approximately 115 kD. Similar to the Drosophila protein, HUGL is part of a cytoskeletal network and, is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates HUGL at serine residues.
 ...
PMID:A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain. 754 63

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.
 ...
PMID:p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3. 758 25

Genetic studies have previously demonstrated cytogenetic deletions and allelic imbalance or loss of heterozygosity (LOH) on the p arm of chromosome 9, in a number of tumour types. We have analysed 45 Non-Small Cell Lung Cancers (NSCLC) with a panel of highly polymorphic microsatellite markers on chromosome 9. Our results indicate that loss on 9p is concentrated within the D9S156-D9S161 region with 44% (20/45) LOH, however the area with minimal loss in this set of lung tumours was found at D9S157 (9p23), with 30% LOH (10/33), whereas loss at the IFNA locus was only found in 6% (2/34) tumours. Five of the lung tumours in this study which demonstrated LOH at D9S157 retained heterozygosity at the adjacent informative markers lying centromeric and telomeric to D9S157. No correlations were found between any of the clinico-pathological parameters and LOH on 9p or at the D9S157 locus. The results of this study indicates the presence of a further putative tumour suppressor gene on 9p at the D9S157 locus (9p23) to be most likely involved in the pathogenesis of non-small cell lung cancer.
 ...
PMID:Loss of heterozygosity at 9p23 defines a novel locus in non-small cell lung cancer. 763 Jun 42

Oncogenesis of tumours related to multiple endocrine neoplasia type 1 (MEN1) is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour suppressor gene in this region. Identification of meiotic cross-overs in MEN1 families has placed the MEN1 locus centromeric of D11S807. An extended deletion mapping was performed in 27 primary parathyroid tumours, and identified D11S427 as the closest centromeric flanking marker. Through physical mapping using newly isolated cDNA clones, we estimated the distance between the flanking markers D11S807 and D11S427 to be less than 900 kb. One of these cDNA clones showed expression of a 4.4 kb message in multiple tissues, including those affected in MEN1, while in five endocrine tumours no transcript was detected. Sequence characterization showed that this gene encodes for the phospholipase C beta 3, a key enzyme in signal transduction.
 ...
PMID:The phospholipase C beta 3 gene located in the MEN1 region shows loss of expression in endocrine tumours. 784 1

We have previously demonstrated allele loss in hamartomas from patients with tuberous sclerosis for markers spanning the tuberous sclerosis gene on chromosome 16q13.3 (TSC2). Germline deletions in the TSC2 gene have been shown in 5% of patients with tuberous sclerosis (TSC). These data support our hypothesis that the TSC2 gene acts as a growth suppressor gene, analogous to the traditional tumour suppressor gene. We now report a TSC hamartoma showing allele loss for markers on chromosome 9q34 in the region of the TSC1 gene. We studied six hamartomas from four sporadic and two familial cases of TSC, none of which showed allele loss for markers on chromosome 16p13.3. The hamartomas were paraffin embedded sections of three renal angiomyolipomas, two giant cell astrocytomas, and a cardiac rhabdomyoma. Eight markers were analysed, comprising from centromeric to telomeric ASS-D9S64-D9S149-ABO-D9S150-DBH-D9S66-D9S67++ +. One angiomyolipoma showed allele loss for the markers ABO, DBH and D9S66, but not for D9S149 or D9S67. The patient was not informative for D9S150. The family structure did not permit the phase of the disease and marker alleles to be determined. These finding support the hypothesis that the TSC1 gene on 9q34, like the TSC2 gene, acts as a growth suppressor. The data would place the TSC1 gene between D9S149 and D9S67. Mapping of allele loss in hamartomas may help in the refinement of the location of the TSC1 locus.
 ...
PMID:The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor. 784 9

Multiple endocrine neoplasia type 1 is an autosomal dominantly inherited disorder predisposing to development of neoplastic lesions in the parathyroid glands, the neuro-endocrine pancreas-duodenum and the anterior pituitary. The genetic defect was mapped to the centromeric region of the long arm of chromosome 11, based on studies of somatic deletions in MEN 1-associated tumours and linkage analysis in affected families. Combined family and tumour analyses have shown that tumourigenesis in MEN 1 involves loss of the wild type chromosome, indicating that the putative MEN 1 gene is a tumour suppressor gene. Based on results from linkage analysis in more than 40 MEN 1 families, presymptomatic testing for MEN 1 using DNA polymorphisms can now be performed with high accuracy. Hence, biochemical screening programmes can focus on individuals at risk, in order to identify early signs of tumour development.
 ...
PMID:Family screening in multiple endocrine neoplasia type 1 (MEN 1). 791 25

A gene for familial melanoma (MLM) has been mapped to 9p22-p13 by linkage analysis using simple tandem repeat polymorphisms (STRPs) at the IFNA and D9S126 loci. This localization is consistent with the finding of homozygous deletions of these markers in DNA from two melanoma cell lines, which suggest that the locus has the properties of a tumour suppressor gene. In an attempt to further define the position of the MLM locus we have typed 10 STRPs from the short arm of chromosome 9 in 15 Australian melanoma kindreds. Extended haplotype analysis of these markers and identification of recombinants in our pedigrees indicate that the MLM gene is flanked on the centromeric side by D9S169 and on the telomeric side by D9S156. These results limit the location of the MLM locus to an interval of about 16 centimorgans.
 ...
PMID:Haplotype analysis limits the position of the familial melanoma locus on 9p to the D9S169-D9S156 interval. 803 15


1 2 3 4 5 6 7 Next >>