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)

Intragenic deletions of TSG101, the human homolog of a mouse gene (tsg101) that acts to suppress malignant cell growth, were reported in human breast tumours. We screened TSG101 for somatic mutations in DNA and RNA samples isolated from a variety of common human malignancies, EBV-immortalised B-cells, and normal lung parenchyma. Intragenic TSG101 deletions in RNA transcripts were frequently found in all types of samples. Analysis of DNA failed to show genomic rearrangements corresponding to transcripts containing deletions in the same samples. The breakpoints of most transcript deletions coincide with genuine or cryptic splice site sequences, suggesting that they result from alternative or aberrant splicing. A similar spectrum of transcript deletions has previously been described in the putative tumour suppressor gene FHIT. We analysed FHIT in the same series of RNA samples and detected truncated FHIT transcripts frequently in both tumour and normal tissues. In addition, transcripts from TSG101, FHIT and seven other genes were analysed in RNA isolated from normal peripheral blood lymphocytes. Large TSG101 and FHIT intragenic transcript deletions were detected and these appeared to be the predominant transcript in 'aged' lymphocytes. Similar alterations were not detected in transcripts of the other genes which were analysed. Our findings demonstrate that truncated TSG101 and FHIT transcripts are commonly detected in both normal and malignant tissues and that a significant fraction of these are likely to be the result of aberrant splicing. While we cannot exclude that alterations in TSG101 and FHIT occur during cancer development, our data indicate that in this context the commonly observed transcript abnormalities are misleading.
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PMID:Aberrant splicing of the TSG101 and FHIT genes occurs frequently in multiple malignancies and in normal tissues and mimics alterations previously described in tumours. 936 28

Recently, a tumour susceptibility gene, TSG101, has been identified at chromosome 11p15. A large intragenic deletion of this gene has been demonstrated in primary breast tumours. To evaluate the role of the TSG101 gene in leukaemia, bone marrow and/or peripheral blood from 68 acute myeloid leukaemia patients, five haemopoietic cell lines (HL60, U937. Raji, KG-1, K562) and 30 normal controls were analysed by reverse transcription of the TSG101 mRNA, followed by PCR amplification and sequencing of the products. The results showed aberrant TSG101 transcripts in 24/68 (35%) acute myeloid leukaemia (AML) patients, all of the cell lines (100%) and 3/30 (10%) normal controls. Our study indicated that the abnormal transcripts may have resulted from aberrant RNA splicing as evidenced by these aberrant transcripts. Also, normal full-length transcripts were present in all specimens examined. The aberrant transcript occurred more frequently in the AML and cell lines. However, because aberrant transcripts of TSG101 were also found in the normal controls, the role of TSG101 as a tumour suppressor gene should be evaluated carefully.
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PMID:Aberrant TSG101 transcripts in acute myeloid leukaemia. 972 3

TSG101 is a recently identified putative tumour suppressor gene which has been implicated in human breast cancer. To address whether germline disruption of TSG101 predisposes individuals to this disease, we analysed genomic DNA and mRNA isolated from peripheral blood from 20 familial breast cancer cases. No evidence of large intragenic insertions/deletions or point mutations in TSG101 was found by Southern blot analysis and sequence analysis of the entire coding region. However, in 11 of 20 samples, 'aberrant' transcripts were detected. Sequence analysis suggested that these variants were generated by the use of different cryptic splicing sites. Such alternative/aberrant splicing events were not restricted to cancer patients, but were also detected in peripheral blood of non-cancer patients and in normal tissues.
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PMID:Truncated TSG101 transcripts are present in peripheral blood from both familial breast cancer patients and controls. 984 57

The candidate tumour suppressor gene TSG101, located on chromosome 11p15, has been associated with frequent intragenic deletion in uncultured primary human breast cancers. Using paired tumour and normal tissues from surgical specimens, we performed nested reverse transcriptase-polymerase chain reaction and direct sequencing to analyse TSG101 exons 1-6 from 32 gastric, 30 colorectal and 16 oesophageal cancers. Truncated transcripts, were found in both tumour and normal tissues from the stomach (15.6 and 12.5%), colon (13.3 and 3.3%) and oesophagus (25 and 25%). Multiple truncated transcripts in individual specimens were also observed. Two types of splicing patterns, one with three to six bases homology at the deletion junction (25.9%), the other with donor site 5' GT and acceptor site 3' AG (55.6%), were the most common patterns. We conclude that in gastrointestinal cancers, truncated transcripts of TSG101 gene occur not uncommonly and do so with a specific splicing pattern.
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PMID:Multiple truncated transcripts of TSG101 in gastrointestinal cancers. 987 Jul 97

A variety of studies suggest that tumour suppressor loci on chromosome 11p are important in various forms of human neoplasia. Recently, a gene located at the chromosome 11p 15.1-15.2 region called TSG101 was discovered and proposed as a candidate tumour suppressor gene in breast cancers. We evaluated the TSG101 gene in a panel of liver cancer cell lines and paired tumours and non-malignant tissues. In this study, four of the seven (57%) cell lines, eight of the 18 (44%) tumours and four of the 18 (22%) non-malignant liver tissues exhibited aberrant TSG101 transcripts by nested reverse transcription-polymerase chain reaction (RT-PCR) analysis. However, a normal-sized transcript without sequence abnormalities verified by single-stranded conformation polymorphism (SSCP) analysis was expressed at robust levels in all the cell lines and most of the tissue samples tested. In addition, Southern blot analysis could identify no genomic abnormalities of the gene. Our results suggest either that the TSG101 gene may not be involved in hepatocarcinogenesis or that it plays a role in the development and/or progress of hepatocellular carcinomas through an unusual mechanism.
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PMID:Analysis of aberrant transcription of TSG101 in hepatocellular carcinomas. 1044 75