Novel MEN1 gene mutations in familial multiple endocrine neoplasia type 1

Sakurai, Akihiro; Shirahama, Shuya; Fujimori, Minoru; Katai, Miyuki; Itakura, Yasunori; Kobayashi, Shinya; Amano, Jun; Fukushima, Yoshimitsu; Hashizume, Kiyoshi

doi:10.1007/s100380050070

Cited by 38 publications

(22 citation statements)

References 12 publications

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“…pcDNA/HisMenin expresses menin tagged with a 35 amino acid polypeptide at its amino terminus and pcDNA/HisMenin516FS expresses tagged mutant menin. This mutation, designated either 1650insC 4) or 1657insC, 7,8) has been identified in patients with MEN 1, and causes a frame shift at amino acid 516 with a new termination codon after amino acid 530. Whole cell extracts of transfected cells were subjected to immunoblotting.…”

Section: Development Of Site-specific Anti-menin Antibodiesmentioning

confidence: 99%

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Characterization of the MEN1 Gene Product, Menin, by Site‐specific Polyclonal Antibodies

Ikeo

Sakurai

Hashizume

1999

Japanese Journal of Cancer Research

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The gene associated with multiple endocrine neoplasia type 1 (MEN 1), designated MEN1, has recently been identified. This gene shows no homology to other known genes, and its expression is not restricted to endocrine organs as estimated by northern blotting. Expression of the MEN1 gene product, menin, has been studied only in a few tissues. In this report, expression of menin in various cells and mouse tissues was studied using two polyclonal antibodies against menin. Expression of menin as a 76 kDa single protein was observed in all cell lines examined, regardless of origin. Two nuclear localization signals of the menin have been reported, but through the study of mutant menin in lymphocytes from subjects with MEN 1, impaired nuclear localization of the mutant menin was observed even though the mutant retained one of the two nuclear localization signals (NLSs). Menin was stable in vitro with a half-life of over 24 h at 37°C. In the cell, the half-life of wild-type menin was about 10 h, while that of the mutant was about 2 h. The mutant rapidly disappeared from the nucleus.

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Section: Development Of Site-specific Anti-menin Antibodiesmentioning

confidence: 99%

“…2,3) Germline mutations of MEN1 have been identified in most subjects with familial and sporadic MEN 1 [2][3][4][5][6][7][8] and in some kindreds with familial hyperparathyroidism. [9][10][11] Somatic MEN1 gene mutations have also been identified in some sporadic parathyroid adenomas, 12) endocrine pancreas tumors 13) and lung carcinoid tumors.…”

mentioning

confidence: 99%

Characterization of the MEN1 Gene Product, Menin, by Site‐specific Polyclonal Antibodies

Ikeo

Sakurai

Hashizume

1999

Japanese Journal of Cancer Research

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“…In the present patient, pathological evidence of primary hyperparathyroidism, which is the most commonlesion in patients with MEN 1 (22), was not obtained by autopsy. However, genetic analysis of the MEN1gene confirmed that the patient was affected with MEN 1 (12).…”

Section: Discussionmentioning

confidence: 96%

“…Direct sequencing of the MEN1gene of the patient and his son revealed a heterozygous 4 base deletion (738del4) in exon 3, which produces a truncated translation product (12). To characterize the pancreas head tumor, several examinations were performed.…”

Section: Case Reportmentioning

confidence: 99%

Chromogranin A Expression in Hepatocellular Carcinoma in a Patient with Germline MEN1 Gene Mutation.

et al. 2000

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Hepatocellular carcinoma (HCC) was found in a patient with multiple endocrine neoplasia type 1 (MEN1). The intriguing finding was that the HCCin the patient was positively stained for chromogranin A(CgA), a cellular marker for endocrine and neuroendocrine tumors. The patient had a pancreas endocrine tumor and type C hepatitis, that made pathological diagnosis of the origin of the tumor complicated.

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“…In addition to these major lesions, several others may also occur, although less frequently, in MEN 1 patients, e.g., adrenal cortical tumors, facial angiofibromas, lipomas, neuroendocrine tumors, thyroid neoplasms, pheochromocytomas, malignant melanomas, and testicular teratomas. The prevalence of MEN 1 syndrome is usually estimated as 1/30,000-1/50,000, but it may be higher in some limited areas (Sakurai et al 1998). The age of onset ranges from 6 to 81 years.…”

Section: Introductionmentioning

confidence: 99%

Unusual presentation of multiple endocrine neoplasia type 1 in a young woman with a novel mutation of the MEN1 gene

et al. 2004

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We report an unusual presentation of multiple endocrine neoplasia type 1 (MEN 1) in a young woman who was subsequently proven to have a novel mutation of the MEN1 gene. The young patient, aged 25 years, was investigated for abdominal discomfort and left upper abdominal pain. Her family history was unremarkable, except an unknown disorder of her father causing early death. Abdominal ultrasonography (USG) and computed tomography revealed a giant pancreatic tumor measuring 10 cm in diameter. The diagnosis of a clinically nonfunctioning pancreatic neuroendocrine tumor was established by clinical and other studies, including USG-guided aspiration biopsy and octreotide scintigraphy, and the patient underwent a distal pancreatectomy. Histology proved a well-differentiated multinodular neuroendocrine tumor of the pancreas. During surgery, a subcutaneous lipoma was also removed from the abdominal wall. Two years later, the patient developed primary hyperparathyroidism, and two enlarged parathyroid glands were surgically removed. Magnetic resonance imaging of the pituitary gland was normal. Screening for MEN1 gene mutation by temperature gradient gel electrophoresis revealed heterozygosities in exons 3, 8, and 9, while direct sequencing indicated a novel germline mutation (C354X) resulting in a stop codon in exon 8 and polymorphisms in exon 3 (R171Q) and exon 9 (D418D and L432L). Genetic screening revealed no mutation in living family members. Our unusual case suggests that a multinodular pancreatic neuroendocrine tumor in a young patient may justify screening for MEN 1 syndrome, even in the absence of other endocrinopathy or family history.

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Novel MEN1 gene mutations in familial multiple endocrine neoplasia type 1

Cited by 38 publications

References 12 publications

Characterization of the MEN1 Gene Product, Menin, by Site‐specific Polyclonal Antibodies

Characterization of the MEN1 Gene Product, Menin, by Site‐specific Polyclonal Antibodies

Chromogranin A Expression in Hepatocellular Carcinoma in a Patient with Germline MEN1 Gene Mutation.

Unusual presentation of multiple endocrine neoplasia type 1 in a young woman with a novel mutation of the MEN1 gene

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