Construction of a 1.2-Mb Sequence-Ready Contig of Chromosome 11q13 Encompassing the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene

Lemmens, Irma; Merregaert, J.; Ven, Wim J.M. Van de; Kas, Koen; Zhang, Chang Xian; Giraud, Sophie; Wautot, Virginie; Buisson, Nathalie; Witte, Ko De; Salandre, Janine; Lenoir, Gilbert; Calender, Alain; Parente, Fabienne; Quincey, Danielle; Courseaux, Anouk; Carle, George F; Gaudray, Patrick; Wit, Mireille J. de; Lips, Cornelis J.M.; Höppener, Jo W.M.; Khodaei, Shideh; Grant, Abby L.; Weber, Günther; Kytölä, Soili; Teh, Bin Tean; Farnebo, Filip; Grimmond, Sean M.; Phelan, Catherine M.; Larsson, Catharina; Forbes, Simon; Bassett, J. H. Duncan; Pannett, A. A. J.; Thakker, Rajesh V.

doi:10.1006/geno.1997.4872

Cited by 32 publications

(18 citation statements)

References 31 publications

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“…Two different large collaborative groups used a positional cloning approach to sequence a MEN1-linked minimal interval that mapped at 11q13 to identify the MEN1 gene (Chandrasekharappa, et al 1997; Guru, et al 1997a; Guru, et al 1997b; Lemmens, et al 1997a; Lemmens, et al 1997b). They showed that the MEN1 gene spans about 9000 bp of genomic DNA containing 10 exons, and transcribed into a 2.8 kb mRNA with the translational start codon (ATG) in exon-2 and the stop codon in exon-10.…”

Section: Positional Cloning Of the Men1 Gene And Identification Of Inmentioning

confidence: 99%

The future: genetics advances in MEN1 therapeutic approaches and management strategies

Agarwal¹

2017

Endocrine-Related Cancer

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The identification of the multiple endocrine neoplasia type 1 (MEN1) gene in 1997 has shown that germline heterozygous mutations in the MEN1 gene located on chromosome 11q13, predisposes to the development of tumors in the MEN1 syndrome. Tumor development occurs upon loss of the remaining normal copy of the MEN1 gene in MEN1-target tissues. Therefore, MEN1 is a classic tumor suppressor gene in the context of MEN1. This tumor suppressor role of the protein encoded by the MEN1 gene, menin, holds true in mouse models with germline heterozygous Men1 loss wherein MEN1-associated tumors develop in adult mice after spontaneous loss of the remaining non-targeted copy of the Men1 gene. The availability of genetic testing for mutations in the MEN1 gene has become an essential part of the diagnosis and management of MEN1. Genetic testing is also helping to exclude mutation negative cases in MEN1 families from the burden of lifelong clinical screening. In the past 20 years, efforts of various groups world-wide have been directed at mutation analysis, molecular genetic studies, mouse models, gene expression studies, epigenetic regulation analysis, biochemical studies, and anti-tumor effects of candidate therapies in mouse models. This review will focus on the findings and advances from these studies to identify MEN1 germline and somatic mutations, the genetics of MEN1-related states, several protein partners of menin, the three-dimensional structure of menin, and menin-dependent target genes. The ongoing impact of all these studies on disease prediction, management and outcomes will continue in the years to come.

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Section: Positional Cloning Of the Men1 Gene And Identification Of Inmentioning

confidence: 99%

The future: genetics advances in MEN1 therapeutic approaches and management strategies

Agarwal¹

2017

Endocrine-Related Cancer

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“…Tumor development is associated with deletion or mutation of the remaining MEN1 allele (1,2). MEN1 mutations have also been reported in a variety of sporadic endocrine tumors including those commonly seen in multiple endocrine neoplasia syndrome type 1 (MEN1) as well as gastric and pulmonary carcinoid tumors (3).…”

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confidence: 99%

Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors

Milne

Hughes

Lloyd

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

416

409

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Mutations in the MEN1 gene are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), which is characterized by parathyroid hyperplasia and tumors of the pituitary and pancreatic islets. The mechanism by which MEN1 acts as a tumor suppressor is unclear. We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MLL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5. Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27 Kip1 and p18 Ink4c . Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27 Kip1 and p18 Ink4c promoters and coding regions. Loss of function of either MLL or menin results in down-regulation of p27 Kip1 and p18 Ink4c expression and deregulated cell growth. These findings suggest that regulation of cyclin-dependent kinase inhibitor transcription by cooperative interaction between menin and MLL plays a central role in menin's activity as a tumor suppressor.MEN1 ͉ methyltransferase ͉ tumor suppressor

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“…M enin is a tumor suppressor encoded by Men1 that is mutated in the human inherited tumor syndrome multiple endocrine neoplasia type 1 (MEN1) (1,2). This syndrome is characterized by tumor development in multiple endocrine organs (3,4).…”

mentioning

confidence: 99%

The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression

Chen

Yan

Keeshan

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

144

171

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Menin is the product of the tumor suppressor gene Men1 that is mutated in the inherited tumor syndrome multiple endocrine neoplasia type 1 (MEN1). Menin has been shown to interact with SET-1 domain-containing histone 3 lysine 4 (H3K4) methyltransferases including mixed lineage leukemia proteins to regulate homeobox (Hox) gene expression in vitro. Using conditional Men1 knockout mice, we have investigated the requirement for menin in hematopoiesis and myeloid transformation. Men1 excision causes reduction of Hoxa9 expression, colony formation by hematopoietic progenitors, and the peripheral white blood cell count. Menin directly activates Hoxa9 expression, at least in part, by binding to the Hoxa9 locus, facilitating methylation of H3K4, and recruiting the methylated H3K4 binding protein chd1 to the locus. Consistent with signaling downstream of menin, ectopic expression of both Hoxa9 and Meis1 rescues colony formation defects in Men1-excised bone marrow. Moreover, Men1 excision also suppresses proliferation of leukemogenic mixed lineage leukemia-AF9 fusionprotein-transformed myeloid cells and Hoxa9 expression. These studies uncover an important role for menin in both normal hematopoiesis and myeloid transformation and provide a mechanistic understanding of menin's function in these processes that may be used for therapy. multiple endocrine neoplasia type 1 ͉ mixed lineage leukemia ͉ Men1 gene ͉ histone lysine methylation

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Construction of a 1.2-Mb Sequence-Ready Contig of Chromosome 11q13 Encompassing the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene

Cited by 32 publications

References 31 publications

The future: genetics advances in MEN1 therapeutic approaches and management strategies

The future: genetics advances in MEN1 therapeutic approaches and management strategies

Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors

The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression

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