Multiple endocrine neoplasia syndromes, children, Hirschsprung's disease and RET

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dc.contributor.authorMoore S.W.
dc.contributor.authorZaahl M.G.
dc.date.accessioned2011-05-15T16:03:45Z
dc.date.available2011-05-15T16:03:45Z
dc.date.issued2008
dc.description.abstractMultiple endocrine neoplasia (MEN) type 2 syndromes are autosomal dominant clinical associations characterized by a common clinical feature, medullary thyroid carcinoma (MTC). The ability to accurately predict the risk by genetic RET proto-oncogene analysis has resulted in the active follow-up of children at risk for developing early metastatic tumours and which can be prevented by prophylactic thyroidectomy. The C634 and M918T mutations (associated with MEN2A and MEN2B, respectively) are particularly associated with early aggressive behavior and distant metastatic spread requiring early intervention. RET is known to be involved in cellular signalling processes during development and controls the survival, proliferation, differentiation and migration of the enteric nervous system (ENS) progenitor cells, as well as the survival and regeneration of sympathetic neural and kidney cells. The centrality of RET in the etiology of both MEN2 and HSCR is now well established with fairly consistent associations existing between RET genotype and phenotype in MEN2. The relationship between Hirschsprung's disease (HSCR) MEN2 syndromes appears to be a highly significant one, sharing a common etiological factor in the RET proto-oncogene. It is now well accepted that most HSCR arises from loss of function, RET mutations, RET haploinsufficiency or RET polymorphisms and haplotypes of the RET promotor region. MEN2 syndromes result from gene up regulation due to germline activating mutations in the RET proto-oncogene (1:500,000). MTC is mostly associated with variations in the 5 cysteine RET radicals and codon-risk management protocols are of considerable value but not infallible. Oncogenic RET mutations may, however, vary between specific population groups. RET analysis in MEN has revolutionized the management of children of MEN2 and allowed surgical prediction and prophylaxis to take place. We discuss the role of genetic testing and possible guidelines for the management of patients from MTC families. The future appears full of promise and the current evaluation of RET-targeting tyrosine kinase and other inhibitors are of considerable interest in the management of these conditions © 2008 Springer-Verlag.
dc.description.versionReview
dc.identifier.citationPediatric Surgery International
dc.identifier.citation24
dc.identifier.citation5
dc.identifier.issn1790358
dc.identifier.other10.1007/s00383-008-2137-5
dc.identifier.urihttp://hdl.handle.net/10019.1/12769
dc.subjectprotein Ret
dc.subjectcancer risk
dc.subjectcell differentiation
dc.subjectcell hyperplasia
dc.subjectcell migration
dc.subjectcell proliferation
dc.subjectcell survival
dc.subjectcodon
dc.subjectdistant metastasis
dc.subjectgene mutation
dc.subjectgenetic polymorphism
dc.subjectgenetic screening
dc.subjectgenetic variability
dc.subjectgenotype phenotype correlation
dc.subjecthaplotype
dc.subjectHirschsprung disease
dc.subjecthuman
dc.subjectmultiple endocrine neoplasia
dc.subjectneurofibromatosis
dc.subjectpriority journal
dc.subjectpromoter region
dc.subjectprotein function
dc.subjectproto oncogene
dc.subjectret oncogene
dc.subjectreview
dc.subjectSipple syndrome
dc.subjectstem cell
dc.subjectthyroidectomy
dc.subjectupregulation
dc.subjectCarcinoma, Medullary
dc.subjectChild
dc.subjectDNA, Neoplasm
dc.subjectGenetic Predisposition to Disease
dc.subjectGenetic Screening
dc.subjectHirschsprung Disease
dc.subjectHumans
dc.subjectMitogens
dc.subjectMultiple Endocrine Neoplasia Type 2a
dc.subjectMutation
dc.subjectProto-Oncogene Proteins c-ret
dc.subjectRisk Factors
dc.subjectThyroid Neoplasms
dc.titleMultiple endocrine neoplasia syndromes, children, Hirschsprung's disease and RET
dc.typeReview
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