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)

The observation of loss of heterozygosity (LOH) in tumours represents a useful clue to the presence of tumour suppressor genes (TSGs). However, analysis of this phenomenon is often complicated by tumour heterogeneity and the presence of DNA from adjacent normal tissues. The present study suggests a quantitative approach for measurement of LOH which may help to distinguish between these possibilities and to provide clues for the heterogeneous process of tumour progression. We applied this methodology to a laryngeal tumour with LOH at markers D9S171, D9S157, D8S87 and THRA1 and found that LOH at D9S171 is the commonest aberration among the tumour cells, while LOH at the THRA1 marker is present in only a small subset of the tumour cells. It is likely that LOH at D9S171 occurs early uin tumour development while LOH at the rest of the markers tested occurred later resulting in the generation of heterogeneous cell populations.
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PMID:Quantitation of the allelic imbalance provides evidence on tumour heterogeneity: a hypothesis. 869 4

Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour suppressor genes. We looked for evidence of microsatellite instability (MI) and LOH on chromosome 7q, 10q, 11p and 17q using seven polymorphic microsatellite markers. In 42 paired breast cancer-peripheral blood DNA samples we identified 24 tumours (57%) exhibiting genetic alterations. Twenty-one specimens exhibited LOH (50%), while 11 specimens exhibited MI (26%) in at least one microsatellite marker. The most frequent incidence of LOH was found for the marker THRA1 (8/33, 24%) indicating that thra I gene becomes a strong candidate tumour suppressor gene, whereas of MI it was D10S109 (3/26, 12%). These MI and LOH data were analysed using a range of clinicopathological parameters. Tumours displaying MI with no evidence of LOH and tumours exhibiting MI and LOH belonging to stage II or III were found, however none were at stage I. These data suggest that MI may be an early event in mammary tumorigenesis whereas LOH occurs at a late stage. A significant association between the absence of oestrogen receptors (p < 0.01) and the absence of both oestrogen and progesterone receptors (p < 0.001) at 17q21 were observed, indicating a possible relationship between specific genetic changes at this region and hormonal deregulation in the progression of breast cancer.
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PMID:Microsatellite instability and loss of heterozygosity in primary breast tumours. 914 12

The molecular genetics of testicular germ cell tumours (TGCT) are still largely unknown. We investigated 20 TGCT tumours for allelic losses (LOH) of tumour supressor genes BRCA1, TP53 and of THRA1 on chromosome 17. We observed an overall loss of 50% for the whole chromosome. Detailed deletion mapping revealed no losses for the BRCA1 gene, 42% LOH for THRA1 and 11% allelic loss for the region telomeric to BRCA1. We observed 11% LOH for TP53. Our results suggest that allelic losses of BRCA1 and TP53 genes do not play a pivotal role in TGCT but that dysfunction of THRA1 or tumour suppressor gene(s) in this region may have an impact in the development of this cancer.
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PMID:Allele loss of tumour suppressor genes on chromosome 17 in human testicular germ cell tumours. 2154 16