The molecular genetics of the multiple endocrine neoplasia syndromes

Thakker, Rajesh

doi:10.1111/j.1365-2265.1993.tb00964.x

Cited by 52 publications

(19 citation statements)

References 62 publications

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“…The development of tumours may be associated with mutations or inappropriate expression of specific normal cellular genes, which are referred to as oncogenes (reviewed in Thakker & Ponder 1988, Thakker 1993, 19941995, Brown & Solomon 1997. Two types of oncogenes, referred to as dominant and recessive oncogenes, have been described.…”

Section: Models Of Tumour Developmentmentioning

confidence: 99%

Multiple endocrine neoplasia type 1.

Pannett¹,

Thakker²

1999

Endocrine-Related Cancer

188

112

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Combined clinical and laboratory investigations of multiple endocrine neoplasia type 1 (MEN1) have resulted in an increased understanding of this disorder which may be inherited as an autosomal dominant condition. Defining the features of each disease manifestation in MEN1 has improved patient management and treatment, and has also facilitated a screening protocol to be instituted. The application of the techniques of molecular biology has enabled the identification of the gene causing MEN1 and the detection of mutations in patients. The function of the protein encoded by the MEN1 gene has been shown to be in the regulation of JunD-mediated transcription but much still remains to be elucidated. However, these recent advances provide for the identification of mutant MEN1 gene carriers who are at a high risk of developing this disorder and thus require regular and biochemical Endocrine-Related Cancer (1999) 6 449-473 screening to detect the development of endocrine tumours.

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Section: Models Of Tumour Developmentmentioning

confidence: 99%

Multiple endocrine neoplasia type 1.

Pannett¹,

Thakker²

1999

Endocrine-Related Cancer

188

112

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“…However, in common with many other tumour types progression to invasive adenoma and the infrequent pituitary carcinoma is thought to be a consequence of a progressive accumulation of genetic abnormalities in these two types of genes which are responsible for controlling cell proliferation and differentiation (Thakker 1993, Melmed 1994. Collectively, numerous studies have put into place some of the changes in both oncogenes and TSGs in pituitary tumorigenesis and have recently been reviewed (Pei & Melmed 1996, Shimon & Melmed 1997, Farrell & Clayton 1998.…”

Section: Mechanisms Responsible For Oncogene and Tumour Suppressor Gementioning

confidence: 99%

Methylation mechanisms in pituitary tumorigenesis.

Farrell

Simpson²,

Frost³

et al. 1999

Endocrine-Related Cancer

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Methylation is essential for embryonic development, however aberrant methylation of CpG islands associated with the tumour suppressor genes (TSGs) and leading to gene silencing is found in numerous tumour types. The TSG p16/CDKN2A is involved in the genesis of many tumour types and frequent methylation of the CpG island of the p16/CDKN2A gene is associated with loss of protein expression in pituitary tumours. In addition, CpG sites are mutational hotspots and abnormal methylation patterns have been shown to lead to genetic instability, predisposing to, and preceding allelic loss. Although several studies of pituitary tumours have shown loss of genetic material at known and putative TSGs loci, studies of the retained alleles have revealed infrequent mutation. Equally, for several other TSGs no mechanisms have been described for their reduced expression. Methylation may represent a unifying theme, responsible in some cases for an absence or reduced expression and in other cases predisposing to allelic loss that may or may not encompass a TSG. In several tumour types treatment of tumours or their cognate cell lines with demethylating agents induces expression of previously methylated genes. Using the mouse corticotroph cell line AtT20 as a model system, transfection studies showed restoration of growth control through induction of ectopically expressed p16/CDKN2A. These effects were reversed by prior in vitro methylation of the constructs' CpG sites within the coding region of this gene. Methylation of an otherwise unmethylated CpG island renders a gene transcriptionally incompetent and clinically these genes represent attractive therapeutic targets since the gene is neither lost nor mutated, but may be reactivated. Future studies will no doubt describe more efficacious pharmacological interventions and identify the mechanisms Endocrine-Related Cancer (1999) 6 437-447 responsible for the abnormal methylation patterns seen in tumours including those of pituitary origin.

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“…MENtype 1, because over 90% of MENtype 1 patients can be diagnosed by the concomitant occurrence of hyperparathyroidism by this age (18). The patient of the present study has been doing well 1 year after the operation and shows no endocrine symptoms.…”

Section: Discussionmentioning

confidence: 48%

Insulin and Somatostatin Releasing Islet Cell Tumor Caused Hypoglycemia.

et al. 2001

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Wereport a hypoglycemic case with normal insulin levels, which was caused by an islet cell tumor that was releasing insulin and somatostatin. Afasting test suggested the over secretion of insulin. Moreover, this hypoglycemiawas enhanced by the inhibitory effect of somatostatin on the secretion of insulin counter-regulatory hormones, such as glucagon, in addition to the autonomoussecretion of insulin from the tumor. In cases of hypoglycemia with apparently normal insulin levels, the measurement of somatostatin and various provocative tests are recommended. Arterial stimulation venous sampling (ASVS)was useful to detect the location of this functioning islet cell tumor. (Internal Medicine 40: 324-330, 2001)

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The molecular genetics of the multiple endocrine neoplasia syndromes

Cited by 52 publications

References 62 publications

Multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1.

Methylation mechanisms in pituitary tumorigenesis.

Insulin and Somatostatin Releasing Islet Cell Tumor Caused Hypoglycemia.

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