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)

In patients with the 3p-syndrome, hemizygous deletion of 3p25-pter is associated with profound growth failure, characteristic facial features, and mental retardation. We performed a molecular genetic analysis of 3p25 breakpoints in four patients with the 3p- syndrome, and a fifth patient with a more complex abnormality, 46,XY,der(3)t(3;?)(p25.3;?). EBV transformed lymphoblasts from each of the patients were initially characterised using fluorescent in situ hybridisation (FISH) and polymorphic microsatellite analyses. The 3p-chromosome from each patient was isolated from the normal chromosome 3 in somatic cell hybrid lines and subsequently analysed with polymorphic and monomorphic PCR amplifiable markers from 3p25. The analysis clearly shows that all five breakpoints are distinct. Furthermore, we have identified yeast artificial chromosomes that cross the 3p25 breakpoints of all four 3p-patients. Two of the patients were deleted for the von Hippel-Lindau (VHL) tumour suppressor gene, although neither has yet developed evidence of VHL disease. The patient with the most centromeric breakpoint, between D3S1585 and D3S1263, had the most severe clinical phenotype including an endocardial cushion defect that was not observed in any of the four patients who had more telomeric breakpoints. This study should provide useful insights into critical regions within 3p25 that are involved in normal human growth and development.
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PMID:Precise localisation of 3p25 breakpoints in four patients with the 3p-syndrome. 893 38

Cytogenetic studies in squamous cell carcinoma of the head and neck (SCCHN) have identified a clustering of breakpoints in a number of chromosomes, including chromosome 3. We have undertaken a loss of heterozygosity analysis (LOH) of 36 SCCHN and six solid tumours which were not squamous cell, and their respective normal specimens, using a bank of microsatellite markers, with the aim of identifying specific sites of frequent loss on chromosome 3. The analysis was undertaken with 12 microsatellite markers, 10 of which are on the p arm of chromosome 3. Allelic loss greater than 10% was seen at four sites; D3S1269 (13%), D3S1079 (23%), D3S659 (23%) and D3S1293 (31%). None of this series of tumours showed loss of the whole chromosome, however 47% of the tumours analysed had LOH at one or more loci. The highest incidence of LOH was found at D3S1293 in the 3p24-p25 region. The second highest region with LOH was found at D3S1079 and D3S659 at 3p13. The remaining markers telomeric and centromeric to these two regions were found to have a LOH of less than 10%. Furthermore, we found a strong association between loss of one marker on chromosome 3 in these SCCHN and poor clinical prognostic indicators; such as site, pathological differentiation, positive nodes at pathology (p<0.05) and TNM status (p<0.05). This study has identified two regions in SCCHN that are most likely to be important in the development of squamous cell carcinoma of the head and neck at 3p24-p25 and 3p13 and may indicate sites of novel tumour suppressor genes in this disease.
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PMID:Allele loss on chromosome-3 in squamous-cell carcinoma of the head and neck correlates with poor clinical prognostic indicators. 2156 56

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary tumour susceptibility disease caused by germline pathogenic variation of the VHL tumour suppressor gene. Affected individuals are at risk of developing multiple malignant and benign tumours in a number of organs.In this report, a male patient in his 20s who presented to the Urologic Oncology Branch at the National Cancer Institute with a clinical diagnosis of VHL was found to have multiple cerebellar haemangioblastomas, bilateral epididymal cysts, multiple pancreatic cysts, and multiple, bilateral renal tumours and cysts. The patient had no family history of VHL and was negative for germline VHL mutation by standard genetic testing. Further genetic analysis demonstrated a germline balanced translocation between chromosomes 1 and 3, t(1;3)(p36.3;p25) with a breakpoint on chromosome 3 within the second intron of the VHL gene. This created a pathogenic germline alteration in VHL by a novel mechanism that was not detectable by standard genetic testing.Karyotype analysis is not commonly performed in existing genetic screening protocols for patients with VHL. Based on this case, protocols should be updated to include karyotype analysis in patients who are clinically diagnosed with VHL but demonstrate no detectable mutation by existing genetic testing.
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PMID:A germline 1;3 translocation disrupting the VHL gene: a novel genetic cause for von Hippel-Lindau. 3306 52