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)

BCL10 is a tumour suppressor gene originally cloned from a t(1;14)(p22;q32) breakpoint in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. Translocations involving this gene, though uncommon, are sometimes encountered in MALT lymphomas. This gene is thought to play an important role in the development of malignant lymphomas. Fluorescence in situ hybridization (FISH) was therefore undertaken on 22 cases of malignant lymphoma of varying histology to establish the incidence of rearrangements involving the BCL10 gene. Initially, one case with a novel t(1;2)(p22;p12) translocation involving the BCL10 gene was identified, in a marginal zone lymphoma of the MALT type, and was reported elsewhere. Seven other cases were subsequently identified with abnormalities in the 1p region, including a translocation with a breakpoint in the 1p22 region in a case of lymphoblastic lymphoma. However, none of these involved the BCL10 gene. Mutation analysis of BCL10 was then performed on 57 cases of malignant lymphoma, including 17 MALT lymphomas, by single-strand conformational polymorphism (SSCP) analysis of tumour DNA. Tissue was obtained for mutation analysis for 12 of the 22 cases analysed by FISH. Selected cases with SSCP band shifts were further studied by direct sequencing. Polymorphisms were identified in eight cases, but no mutations of pathogenic significance were identified. Further RT-PCR and mutation analysis was performed on cDNAs from 12 cases (four MALT, seven diffuse large B-cell lymphoma, one Hodgkin's disease) in which DNA analysis had already been completed. This included the MALT lymphoma with the t(1;2)(p22;p12) rearrangement. Again, no mutations were identified in the coding sequence. This study confirms that rearrangements of the BCL10 gene are uncommon in lymphoma (1/22) and may be limited tothe MALT subtype of non-Hodgkin's lymphomas. It was also found that breakpoints or rearrangements in the 1p22 region do not necessarily involve the BCL10 gene. Moreover, the absence of mutations at both the DNA (0/60) and the mRNA (0/12) level indicates that this gene is not frequently inactivated by mutation, in those tumours in which it is not involved in translocations. Our findings suggest that the BCL10 gene is unlikely to have a frequent or key role in general lymphomagenesis.
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PMID:BCL10 in malignant lymphomas--an evaluation using fluorescence in situ hybridization. 1174 43

Hereditary multiple exostoses is an autosomal dominant disorder characterised by the presence of multiple osteochondromas, resulting in a variety of skeletal deformities. It is a genetically heterogeneous condition for which two genes, EXT1 and EXT2, have been isolated. The EXT1 gene, located at 8q24, has been shown to harbour mutations in 44-66% of the hereditary multiple exostoses-families. Mutations in the EXT2 gene, located at 11p11-p12, are detected in about 30% of the families. Additional linkage to chromosome 19p suggests the existence of an EXT3 gene. EXT1 has been shown to act as a tumour suppressor gene in hereditary multiple exostoses, resulting in osteochondroma formation when both copies of EXT1 are lost. Diagnostic germ-line mutation analysis is operative in the Clinical Genetic Center Leiden, the Netherlands.
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PMID:[From gene to disease; hereditary multiple exostoses]. 1184 65

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is dependent on Helicobacter pylori infection. Bacterial colonisation of the gastric mucosa triggers lymphoid infiltration and the formation of acquired MALT. The bacterial infection induces and sustains an actively proliferating B-cell population through direct (autoantigen) and indirect (intratumoral T cells specific for H. pylori) immunological stimulation. Moreover, the bacterial infection provokes a neutrophilic response, which causes the release of oxygen free radicals. These reactive species may promote the acquisition of genetic abnormalities and malignant transformation of reactive B cells. A transformed clone carrying the translocation t(1;18)(q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. Malignant clones without t(11;18)(q21;q21), but with other genetic abnormalities, such as trisomy 3 or microsatellite instability, depend critically on immune stimulation mediated by H. pylori for their clonal expansion. In the early stages, the tumour can be successfully treated by eradication of the bacterium, whereas at later stages the tumour may escape its growth dependency through acquisition of additional genetic abnormalities such as t(1;14)(p22;q32) and t(1;2)(p22,p12) involving the BCL-10 gene. Finally, further genetic abnormalities, such as inactivation of the tumour suppressor genes, p53 and p16, can lead to high-grade transformation. Detection of these abnormalities may help with the clinical management of patients with gastric MALT lymphoma.
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PMID:Gastric MALT lymphoma: from aetiology to treatment. 1190 29

Loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour suppressor genes. We have undertaken extensive allelotyping of 45 specimens of non-small cell lung cancer (NSCLC) using 92 polymorphic microsatellite markers on 39 chromosome arms. The most frequent allelic imbalances were found on chromosome arms 3p, 9p and 17p. Significant allelic imbalance was found on other chromosome arms including, 5q (21%), 8p (19%), 13q (24%) and 17q (18%). The LOH data on 3p was subdivided into the four chromosomal regions considered to contain putative tumour suppressor genes 3p25-p24 (10%), 3p21 (10%), 3p14 (25%) and 3p13-p12 (22%). The frequency of loss in the different regions on 9p were: 9pter-p23 (31%), 9p23-p22 (45%) and 9p21-cent (30%). LOH on 17p was separated into three regions: 17pter-p13 (9%), 17p13 (33%) and 17p13-cent (22%). No correlation was found between LOH on any of the chromosomal arms and any of the clinicopathological parameters such as pathology, level of differentiation, TNM staging or alcohol intake. Only one significant association was found between LOH and tumour types. A significant difference was found between LOH on 17q in adenocarcinomas and squamous cell carcinomas (p=0.037). The fractional allele loss (FAL) values for this group of 45 NSCLC gave a median value of 0.9 (range 0-0.45). No correlation was found between FAL and nodes at pathology (p>0.05) and between FAL and tumour grade (p>0.05). No correlation was found between p53 or ras mutations in these NSCLC specimens and their FAL values. Accumulated genetic damage, as provided by this allelotype analysis, provides a useful molecular parameter by which to assess NSCLC and may, in time, assist in the determination of the clinical behaviour and clinical outcome of these tumours.
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PMID:Allelotype of non-small cell lung cancer. 2154 47