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)

Loss of heterozygosity (LOH) at loci on chromosome 9p and/or 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder. However, localisation of the tumour suppressor locus or loci on 9q has been hampered by the relative infrequency of tumours with subchromosomal deletions. We have used 24 microsatellite markers to examine LOH in 70 new cases of TCC of the bladder and upper urinary tract. Forty tumours (57%) showed LOH at one or more loci on 9q and partial deletions were detected in five tumours (7%). Combined data from the five cases with partial deletions place one tumour suppressor locus at 9q34 between D9S61 and D9S66 (an estimated distance of 13-14 cM). This region is frequently deleted in other sporadic tumours and encompasses one of the loci for tuberous sclerosis (TSC1). One tumour contained a distinct deletion between D9S153 and D9S109 (9q13-q31), which encompasses the locus for the familial nevoid basal cell carcinoma syndrome (Gorlin syndrome). This may indicate the presence of another tumour suppressor locus on 9q for TCC. Our findings significantly reduce the regions of 9q within which suppressor genes for TCC may reside. The possible involvement of two deletion targets on 9q in addition to the locus at 9p21 implicated in TCC may explain why LOH at all loci on chromosome 9 is frequent in TCC.
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PMID:Detailed deletion mapping of chromosome 9q in bladder cancer: evidence for two tumour suppressor loci. 747 93

Although the aetiology of common skin cancer, basal cell carcinoma (BCC), is unknown, epidemiological findings suggest that, in addition to genetic predisposition, excessive exposure to UV-light, especially in the form of episodes of intensive sunburn, is a crucial aetiological factor. Biologically, BCC may vary from superficial, relatively benign tumours to aggressive infiltrating tumours. Hereditary BCC (Gorlin's syndrome) is most probably caused by inactivation of a tumour suppressor gene on chromosome 9q, and recent findings suggest that this gene may also be involved in common sporadic cases of BCC.
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PMID:[Basal cell cancer--current research sheds new light]. 789 23

The human growth-arrest specific gene GAS1 maps to chromosome bands 9q21.3-->q22, the region known to contain the tumour suppressor gene responsible for nevoid basal cell carcinoma syndrome (NBCCS). Because of its putative action as a tumour suppressor gene, the GAS1 gene was analysed as a candidate for the NBCCS gene. Using two-colour fluorescence in situ hybridization, the GAS1 gene maps outside the interval which, by genetic analysis, has been shown to contain the NBCCS gene.
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PMID:The human growth-arrest-specific gene GAS1 maps outside the candidate region of the gene for nevoid basal cell carcinoma syndrome. 795 49

The human cdk2/cyclin A kinase complex is a key regulator of the events of S phase. This complex contains several proteins involved in regulating its catalytic activity, including one or more of the CKS proteins, which have recently been shown to inhibit the activation of the cdk2 kinase. To investigate whether the CKS genes may be altered in human neoplasia, we mapped the chromosome locations of CKS1 and CKS2 by fluorescence in situ hybridization (FISH). CKS1 was localized to 8q21, a locus that is seldom grossly altered in cancer. The localization of CKS2 to 9q22 places it very near to a putative tumour suppressor locus suggested to be responsible for susceptibility to the Basal Cell Nervus Syndrome (BCNS or Gorlin's syndrome) familial cancer disorder. Six fibroblast cell lines isolated from patients with BCNS were demonstrated by FISH to have both copies of CKS2 present. Partial sequencing of a genomic clone of CKS2 revealed that the open reading frame lies over three exons. Examination of the six cell lines by SSCP and PCR-based sequencing of the parts of the three exons coding for the full length protein demonstrated no consistent divergence from the reported cDNA sequence in any exon. It is unlikely that CKS2 is the BCNS tumour suppressor gene.
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PMID:Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22. 869 18

Basal cell carcinoma (BCC) is the most common cancer in humans. The majority of sporadic BCCs have allele loss on chromosome 9q22 implying that inactivation of a tumour suppressor in this region is an important step in BCC formation. The gene for nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder characterized by multiple BCCs, maps to the same region and is presumed to be the tumour suppressor inactivated at this site. NBCCS has been identified recently and encodes a protein with strong homology to the Drosophila segment polarity gene, patched. Analysis of Drosophila mutants indicates that patched interacts with the hedgehog signalling pathway, repressing the expression of various hedgehog target genes including wingless, decapentaplegic and patched itself. Using single strand conformational polymorphism (SSCP) to screen human patched in 37 sporadic BCCs, we detected mutations in one-third of the tumours. Direct sequencing of two BCCs without SSCP variants revealed mutations in those tumours as well suggesting that inactivation of patched is probably a necessary step in BCC development. Northern blots and RNA in situ hybridization showed that patched is expressed at high levels in tumour cells but not normal skin suggesting that mutational inactivation of the gene leads to overexpression of mutant transcript owing to failure of a negative feedback mechanism.
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PMID:The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. 878 9

Mutation of the p53 tumour suppressor gene can produce a more stable protein that does not inhibit mitosis, accumulates in the nucleus and can then be detected immunohistochemically in many human tumours using antibody CM-1. The protein has also been detected in odontogenic keratocysts. Routinely processed material from 30 odontogenic keratocysts was immunostained with antibody CM-1. Ten were recurrences and five were associated with the basal-cell naevus syndrome (Gorlin-Goltz syndrome). p53 protein was found in 50% (15/30) of the odontogenic keratocysts, in 53.3% (8/15) of non-recurrent cysts, in 40% (4/10) of recurrent cysts and in 60% (3/5) of those associated with the basal-cell naevus syndrome. Staining was weak and speckled and limited to occasional basal and suprabasal cells. There was no statistically significant difference in staining between these groups and no correlation between expression and the presence of satellite cysts, basal-cell budding or islands of odontogenic epithelium. The low levels of expression may represent physiological expression of wild-type p53 protein rather than mutant or complexed p53 protein.
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PMID:p53 immunohistochemistry of odontogenic keratocysts in relation to recurrence, basal-cell budding and basal-cell naevus syndrome. 885 Jun 45

Gorlin's syndrome embraces a constellation of cranial, maxillofacial and systemic disorders, which may have a serious effect on both the morbidity and mortality of the patients. Recent work has identified that the disorder is caused by a mutation within a tumour suppressor gene.
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PMID:Gorlin's syndrome: main features and recent advances. 890 12

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder, characterized by predisposition to multiple early basal cell carcinomas of the skin and several other tumours as well as frequent occurrence of developmental anomalies. The gene has previously been mapped to chromosome 9q22 and is believed to function as a tumour suppressor. We have applied linkage and haplotype analysis to four Swedish nevoid basal cell carcinoma syndrome families to refine the localization of the nevoid basal cell carcinoma syndrome gene. Information from critical recombinants localizes the gene proximal of marker D9S287, which in combination with analysis of loss of heterozygosity in a hereditary cardiac fibroma has allowed us to define a minimal candidate region of 1Mb or less for the nevoid basal cell carcinoma gene flanked by the markers D9S280 and D9S287 in the 9q22.3 area.
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PMID:Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q. 905 67

Individuals with naevoid basal cell carcinoma (Gorlin) syndrome are at increased risk of developing medulloblastoma in childhood. We have shown that approximately 5% of patients with Gorlin syndrome will develop this complication in the first few years of life, and in addition 10% of patients with medulloblastoma diagnosed at age 2 years or under have Gorlin syndrome. One out of three medulloblastomas occurring in patients with Gorlin syndrome was shown to have lost the wild-type allele on 9q, indicating that the Gorlin locus probably acts as a tumour suppressor in the development of this tumour. We have also confirmed this role in a basal cell carcinoma (BCC) from the same individual. Information from these families would suggest that Gorlin syndrome is more common than previously recognized and may not always be diagnosed on clinical grounds alone even in middle life.
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PMID:The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. 923 11

Mutations of the human Patched gene ( PTCH ) have been identified in individuals with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in sporadic basal cell carcinomas and medulloblastomas. We have isolated a homologue of this tumour suppressor gene and localized it to the short arm of chromosome 1 (1p32.1-32.3). Patched 2 ( PTCH2 ) comprises 22 coding exons and spans approximately 15 kb of genomic DNA. The gene encodes a 1203 amino acid putative transmembrane protein which is highly homologous to the PTCH product. We have characterized the genomic structure of PTCH2 and have used single-stranded conformational polymorphism analysis to search for mutations in PTCH2 in NBCCS patients, basal cell carcinomas and in medulloblastomas. To date, we have identified one truncating mutation in a medulloblastoma and a change in a splice donor site in a basal cell carcinoma, suggesting that the gene plays a role in the development of some tumours.
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PMID:Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32. 993 36


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