Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states

Agarwal, Sunita

doi:10.1093/hmg/6.7.1169

Cited by 433 publications

(310 citation statements)

References 19 publications

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“…This was contradictory to the previous report showing that no mutation of the MEN1 gene was detected in 5 probands with FHP in the United States and Canada [10]. On the other hand, it has recently been reported that a Japanese patient with FHP had a germline mutation of the MEN1 gene (Y353X in exon 8), although the clinical evaluation for MEN1 was not described in this family [13].…”

Section: Discussioncontrasting

confidence: 99%

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Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

et al. 1998

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Abstract. Familial primary hyperparathyroidism(FHP) is a rare hereditary disorder characterized by isolated parathyroid tumors without any other lesions related to multiple endocrine neoplasia (MEN). Primary hyperparathyroidism is usually expressed at an early age and is highly penetrated in MEN type 1(MEN1), suggesting that some FHP may be a variant type or early stage of MEN1. The MEN1 gene has recently been cloned and its germline mutations have been considered to play an important role in the tumorigenesis of MEN1. We studied a Japanese family with primary hyperparathyroidism which included 4 patients. To investigate the possible relationship between primary hyperparathyroidism in this family and the MEN1 gene, we analyzed a proband for a germline mutation of the MEN1 gene in this study. We identified a novel heterozygous mutation (1350de13) at codon 414 in exon 9. Restriction digestion analysis revealed the same mutation pattern in his brother with hyperparathyroidism. These findings suggest that our patients may belong to a variant type of MEN1.

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Section: Discussioncontrasting

confidence: 99%

“…This gene contains 10 exons and encodes a 610 amino acid protein [9]. It has been reported that germline heterozygous mutations of the MEN1 gene are closely related to the endocrine tumorigenesis in MEN1 [10,11]. If a germline mutation of the MEN1 gene was found in a FHP …”

Section: Familial Primary Hyperparathyroidismmentioning

confidence: 99%

Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

et al. 1998

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“…Each patient met clinical criteria for MEN1 6 and had a MEN1 germline mutation 16 (Table 1). Endocrine and mesenchymal MEN1 tumor manifestations included multiple parathyroid tumors, gastrinomas and metastases, pancreatic neuroendocrine tumors, lung carcinoids, lipomas, and angiofibromas.…”

Section: Patients and Tumorsmentioning

confidence: 99%

Multiple Leiomyomas of the Esophagus, Lung, and Uterus in Multiple Endocrine Neoplasia Type 1

McKeeby

Zhuang

et al. 2001

The American Journal of Pathology

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Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder characterized by multiple parathyroid, pancreatic, duodenal, and pituitary neuroendocrine tumors. Nonendocrine mesenchymal tumors, such as lipomas, collagenomas, and angiofibromas have also been reported. MEN1-associated neuroendocrine and some mesenchymal tumors have documented MEN1 gene alterations on chromosome 11q13. To test whether the MEN1 gene is involved in the pathogenesis of multiple smooth muscle tumors, we examined the 11q13 loss of heterozygosity (LOH) and clonality patterns in 15 leiomyomata of the esophagus, lung, and uterus from five patients with MEN1. Forty sporadic uterine leiomyomata were also studied for 11q13 LOH. LOH analysis was performed using four polymorphic DNA markers at the MEN1 gene locus; D11S480, PYGM, D11S449, and INT-2. The gene for multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant tumor syndrome, has been mapped to chromosome 11q13 1 and recently identified. 2 The MEN1 gene is thought to act as a tumor suppressor based on the presence of inherited inactivating mutations in the constitutional DNA of affected family members accompanied by the loss of the wild-type allele in associated tumors. 2-4 Somatic inactivation of the MEN1 gene has been also documented in a subset of sporadic counterpart parathyroid, enteropancreatic, and pulmonary endocrine tumors, and mesenchymal tumors. 5 MEN1 patients typically present first with primary hyperparathyroidism resulting from multiple parathyroid tumors caused by MEN1 gene alterations. 6 Neuroendocrine tumors of the pancreas, duodenum, anterior pituitary gland, stomach, and lung are other tumors that are an integral part of MEN1. 7,8 Nonendocrine mesenchymal tumors, such as lipomas, angiofibromas, and collagenomas, have also been shown to be associated with MEN1 and MEN1 gene alterations. 8 -10 Leiomyomata have been occasionally documented in MEN1 patients, 8,[11][12][13][14] and loss of heterozygosity (LOH) at the MEN1 locus was recently shown in two esophageal leiomyomata from one MEN1 patient. 15 MEN1 gene inactivation in lung or uterine leiomyomata, however, has not been studied. To test whether MEN1 gene alterations are involved in the development of multiple smooth muscle tumors in MEN1 patients, we analyzed 15 leiomyomata from five patients with documented MEN1 germline mutations for LOH at the MEN1 gene locus. To assess whether MEN1 gene alterations are present in sporadic smooth muscle tumors, we analyzed 40 sporadic uterine leiomyomata for MEN1 gene deletion for comparison. Furthermore, to evaluate whether MEN1-associated leiomyomata arise as independent clonal events at different anatomical sites within an organ, the patterns of 11q13 LOH in different tumors from individual patients

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“…1 Menin interacts with a wide number of proteins involved in transcriptional regulation, genome stability, cell division, and proliferation. 2 Germline mutations of the MEN1 gene along with the loss of heterozygosity (LOH) result in menin structural changes and subsequent loss of tumor-suppressing function. 3 As for many other tumor suppressor genes, there is no genotype-phenotype correlation in MEN1.…”

Section: Introductionmentioning

confidence: 99%

A MEN1 syndrome with a paraganglioma

et al. 2013

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Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1. We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGG-AAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL.

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Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states

Cited by 433 publications

References 19 publications

Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

Germline Mutation of the Multiple Endocrine Neoplasia Type 1(MEN1) Gene in a Family with Primary Hyperparathyroidism.

Multiple Leiomyomas of the Esophagus, Lung, and Uterus in Multiple Endocrine Neoplasia Type 1

A MEN1 syndrome with a paraganglioma

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