Multiple Endocrine Neoplasia Type 2

Gagel, Robert F.; Shefelbine, Sarah; Hayashi, Hironori; Cote, Gilbert J.

doi:10.1007/978-1-59259-963-9_40

Cited by 18 publications

(34 citation statements)

References 48 publications

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“…In the present case, successful parathyroidectomy lowered serum Ca levels (from 1 1.6 to 9.3 mg/ dl), which also led to reduced serum gastrin levels (from 310 to 120 pg/ml). Recently it is commonly accepted that autogenous grafting of parathyroid tissue to the forearm is beneficial in the management of parathyroid hyperplasia (20). The high rate of recurrence in MEN1 patients does not argue against the use of such autogenous grafts (20), since there is a significant advantage in being able to removethe enlarged tumor under local anesthesia.…”

Section: Discussionmentioning

confidence: 99%

“…Recently it is commonly accepted that autogenous grafting of parathyroid tissue to the forearm is beneficial in the management of parathyroid hyperplasia (20). The high rate of recurrence in MEN1 patients does not argue against the use of such autogenous grafts (20), since there is a significant advantage in being able to removethe enlarged tumor under local anesthesia. This autogenous graft has been shownto control serum Ca levels more efficiently in patients with MEN1 (21).…”

Section: Discussionmentioning

confidence: 99%

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A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

Wada

Watanabe

Tsukada³

et al. 2001

Intern. Med.

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Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by tumors of the enteropancreas, parathyroid and anterior pituitary. The MEN1 gene was recently cloned, and germline mutations of the gene have been demonstrated in cases of MEN 1. Here, we report a Japanese family with a germline mutation of the MEN1 gene. The proband (44 y.o., male) had primary hyperparathyroidism (PHP) and pancreatic carcinoid, and his older sister (50 y.o.) had a history of parathyroidectomy for primary hyperparathyrodism at the age of 40. Clinical examination revealed no evidence of PHPor other MEN1-related tumors in his son. Direct sequencing analysis revealed a heterozygous germline mutation (lOOldelC) at codon 297 in exon 6 of the MEN1 gene in the proband and his son. Loss of heterozygosity (LOH) was also found in the resected parathyroid tissue of the proband. The deletion of cytosine 1001 observed in this case induces a frame shift, which causes the appearance of a stop codon (TAG) at codon 367. This mutation appears to be associated with tumors of the endocrine tissues in the cases studied. (Internal Medicine 40: 499-505, 2001)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

Wada

Watanabe

Tsukada³

et al. 2001

Intern. Med.

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“…RET mutation analysis is largely exploited to optimize the diagnostic and clinical management of hereditary MTC (Chiefari et al 1998, Marx 2005, Gagel & Marx 2008. The presence of a known MEN2-associated RET mutation in the germline of an MTC patient identifies hereditary MTC disease, thus allowing preclinical identification of family members at risk of developing MTC, as well as providing information about the risk of the proband developing other tumors associated with MEN2 syndromes.…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of the MTC-associated germline RET-K666E mutation: evidence of oncogenic potential enhanced by the G691S polymorphism

Borrello¹,

Aiello²,

Peissel³

et al. 2011

Endocrine-Related Cancer

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Activating mutations of RET, a gene encoding two isoforms of a tyrosine kinase receptor physiologically expressed in several neural crest-derived cell lineages, are associated with the inherited forms of medullary thyroid carcinoma (MTC). The identification and characterization of novel RET mutations involved in MTC is valuable, as RET gene testing plays a crucial role in the management of these patients. In an MTC patient, we have identified a germline c.1996AOG transition in heterozygosis leading to K666E substitution. In addition, the conservative S904S (c.2712COG) and the non-conservative functional G691S (c.2071GOA) polymorphisms have been identified. Through functional studies, we demonstrate for the first time that K666E is a gain-of-function mutation with oncogenic potential, based on its ability to transform NIH3T3 cells. It was not possible to define whether K666E is a de novo or inherited RET variant in the patient, as the family history was negative for MTC, and the carrier status of family members could not be tested. Our results, together with a recent report of co-segregation of the mutation in three MTC families, suggest that K666E is a causative MTC mutation. As we have shown that the same patient allele carries both K666E and G691S variants, the latter known to increase downstream RET signaling, a possible role for the G691S polymorphism has also been investigated. We have demonstrated that, although RET-G691S is not oncogenic per se, it enhances the transforming activity of the RET-K666E mutant, thus suggesting a modifier role for this functional polymorphism.

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“…MULTIPLE endocrine neoplasia type 1 (MEN1) is a hereditary disease characterized by hyperplastic and neoplastic disorder of endocrine organs such as parathyroid, anterior pituitary and gastroenteropancreatic endocrine tissues [1]. The responsible gene (MEN1) has been mapped to 11q13 [2] and later identified by positional cloning [3,4].…”

mentioning

confidence: 99%

“…The responsible gene (MEN1) has been mapped to 11q13 [2] and later identified by positional cloning [3,4]. Most subjects with MEN1 harbor a germline MEN1 gene mutation, and somatic mutations of the MEN1 gene have been identified in sporadic endocrine tumors to some extent [1]. Mutation of the MEN1 gene along with the loss of the unaffected allele in the tumor of patients indicates that this gene functions as a tumor suppressor and the loss of both alleles leads to tumor development [5].…”

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confidence: 99%

JunD-Menin Interaction Regulates c-Jun-mediated AP-1 Transactivation

et al. 2004

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Abstract. The gene responsible for multiple endocrine neoplasia type 1, MEN1, encodes the 610-amino acid-protein, menin. Although menin has been reported to bind AP-1 transcription factor JunD and suppress its transcriptional activity, little is known about its molecular mechanisms and physiological role. To better understand the function of menin and its significance in tumorigenesis, we investigated the effect of wild-type and mutant menin proteins on AP-1 transactivation. In COS cells, wild-type menin suppressed JunD-mediated transactivation in a dose-dependent manner, while it augmented c-Jun-mediated transactivation also in a dose-dependent manner. These effects were lost or reduced in all menin mutants examined. Electrophoretic mobility shift assay using AP-1 binding elements as a probe revealed that menin does not affect binding of c-Jun to DNA. Coexpression of menin mutants did not affect the function of wild-type menin. Coexpression of JunD amino-terminal fragment abolished menin-mediated enhancement of c-Jun transactivation, suggesting that Menin-JunD interaction may negatively regulate the enhancing effect of menin on c-Jun-mediated transactivation in COS cells.

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Multiple Endocrine Neoplasia Type 2

Cited by 18 publications

References 48 publications

A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.

Functional characterization of the MTC-associated germline RET-K666E mutation: evidence of oncogenic potential enhanced by the G691S polymorphism

JunD-Menin Interaction Regulates c-Jun-mediated AP-1 Transactivation

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