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

FHIT, a candidate tumour suppressor gene, has recently been identified at chromosomal region 3p14.2, and deletions of the gene have been reported in many types of human cancers. Loss of heterozygosity (LOH) at this region has also been found frequently in follicular thyroid carcinoma (FTC). To investigate the potential role of FHIT in thyroid tumorigenesis, we examined 57 thyroid tumour specimens (eight benign adenomas, 40 papillary, four follicular and five anaplastic carcinomas), and two thyroid carcinoma cell lines (NPA, SW579) for genetic alterations by using reverse transcription-polymerase chain reaction (RT-PCR), PCR product sequencing, single-strand conformation polymorphism (SSCP) and Southern blot analysis. Two cervical carcinoma cell lines (C-33A, HeLa) were included as positive controls. We detected truncated FHIT transcripts in three of eight (38%) benign adenomas, nine of 40 (23%) papillary, and two of five (40%) anaplastic carcinomas, and in three cell lines (SW579, C-33A, HeLa). Most of the truncated transcripts lacked exons 4 or 5 to 7 or 8 of the gene and were presumably non-functional as the translation start site is located in exon 5. SSCP analysis of the coding exons failed to detect any point mutations among the samples without abnormal FHIT transcripts. Southern blot analysis demonstrated either loss or reduced intensity of major Bam HI restriction fragments in the three cell lines found to have abnormal FHIT transcripts, indicating, respectively, either intragenic homozygous or heterozygous deletions of the FHIT gene. Intragenic homozygous deletions were also found in two papillary thyroid carcinoma specimens: one was missing a 13 kb Bam HI fragment which contains exon 4, the other had deletions of 15.5, 13 and 4.2 kb fragments which contain exons 2 and 9, 4, and 5, respectively. The absence of a defective FHIT gene in FTC indicates that an additional tumour suppressor gene may reside in this region and be involved in the development of FTC. Given that defective FHIT genes were found in both benign and malignant thyroid tumours, the inactivation of this putative tumour suppressor gene is likely to be an early event in the pathogenesis of some forms of thyroid neoplasms.
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PMID:FHIT gene abnormalities in both benign and malignant thyroid tumours. 1044 1