Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Germline mutations in the fumarate hydratase gene at 1q43 predispose to dominantly inherited skin and uterine leiomyomata and leiomyosarcomas. The enzyme, which is a component of the tricarboxylic acid cycle, acts as a tumour suppressor. To evaluate fumarate hydratase in respective sporadic tumours, we analysed a series of 26 leiomyosarcomas and 129 uterine leiomyomas (from 21 patients) for somatic mutations in fumarate hydratase and allelic imbalance around 1q43. None of the 26 leiomyosarcomas harboured somatic mutations in fumarate hydratase. Fifty per cent of leiomysarcomas tested showed evidence of allelic imbalance at 1q, but this was not confined to the vicinity of fumarate hydratase. Only 5% (seven out of 129) of the leiomyomas showed allele imbalance at 1q42-q43 and no somatic mutations in fumarate hydratase were observed. Our findings indicate that mutations in fumarate hydratase do not play a major role in the development of sporadic leiomyosarcomas or uterine leiomyomas
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PMID:Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas. 1217 82

Multiple cutaneous and uterine leiomyomata (MCL) is an autosomal dominant disorder characterized by the development of benign smooth muscle tumours (leiomyomas) in the skin and uterus of affected women, and in the skin of affected men. In rare cases, MCL has been associated with a predisposition to the rare type II papillary renal cell cancer, also known as hereditary leiomyomatosis and renal cell cancer. The genetic locus for MCL has been mapped to chromosome 1q42.3-43 and subsequently, germline mutations in the fumarate hydratase (FH) gene have been identified. In addition, analysis of FH in some tumours of MCL patients revealed a second mutation inactivating the wild-type allele, suggesting that FH may function as a tumour suppressor gene. Here, we report two cases of MCL patients with FH mutations, designated as T287P and R190L. T287P represents a novel mutation of a highly conserved amino acid of the FH protein. In addition, a patient with an unusual clinical presentation of MCL was found to have the recurrent mutation, R190L, raising the possibility of incorporating FH sequencing as a diagnostic tool. Our findings extend the allelic series of mutations in FH and support its status as the underlying cause of MCL.
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PMID:Multiple cutaneous and uterine leiomyomata resulting from missense mutations in the fumarate hydratase gene. 1630

Uterine fibroids are the most common benign tumour of the female genital tract. However, their true prevalence is probably under-estimated, as the incidence at histology is more than double the clinical incidence. Recent longitudinal studies have estimated that the lifetime risk of fibroids in a woman over the age of 45 years is more than 60%, with incidence higher in blacks than in whites. The cause of fibroids remains unclear and their biology poorly understood. No single candidate gene has been detected for commonly occurring uterine fibroids. However, the occurrence of rare uterine fibroid syndromes, such as multiple cutaneous and uterine leiomyomatosis, has been traced to the gene that codes for the mitochondrial enzyme, fumarate hydratase. Cytogenetic abnormalities, particularly deletions of chromosome 7, which are found in up to 50% of fibroid specimens, seem to be secondary rather than primary events, and investigations into the role of tumour suppressor genes have yielded conflicting results. The key regulators of fibroid growth are ovarian steroids, both oestrogen and progestogen, growth factors and angiogenesis, and the process of apoptosis. Black race, heredity, nulliparity, obesity, polycystic ovary syndrome, diabetes and hypertension are associated with increased risk of fibroids, and there is emerging evidence that familial predisposition to fibroids is associated with a distinct pattern of clinical and molecular features compared with fibroids in families without this prevalence.
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PMID:Incidence, aetiology and epidemiology of uterine fibroids. 1853 13