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Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene.
J Intern Med. 1998 Jun; 243(6):433-9.JI

Abstract

For nearly a decade since the mapping of the multiple endocrine neoplasia type 1 (MEN1) locus to 11q13 and the suggestion that it is a tumour suppressor gene, efforts have been made to identify the gene responsible for this familial cancer syndrome. Recently, we have identified the MEN1 gene by the positional cloning approach. This effort involved construction of a 2.8-Mb physical map (D11S480-D11S913) based primarily on a bacterial clone contig. Using these resources, 20 new polymorphic markers were isolated which helped to reduce the interval for candidate genes by haplotype analysis in families and by loss of heterozygosity (LOH) studies in approximately 200 tumours, utilizing laser-assisted microdissection to obtain tumour cells with minimal or no admixture by normal cells. The interval was narrowed by LOH to only 300 kb, and nearly 20 new transcripts that map to this region of 11q13 were isolated and characterized. One of the transcripts was found by dideoxyfingerprinting and cycle sequencing to harbour deleterious germline mutations in affected individuals from MEN-1 kindreds and therefore identified as the MEN1 gene. The type of germline mutations and the identification of mutations in sporadic tumours support the Knudson's two-hit model of tumorigenesis for MEN-1. Efforts are being made to identify the function of the MEN1 gene-encoded protein, menin, and to study its role in tumorigenesis.

Authors+Show Affiliations

Genetics and Molecular Biology Branch, NHGRI, National Institutes of Health, Bethesda, MD 20892-4442, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9681840

Citation

Guru, S C., et al. "Identification and Characterization of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene." Journal of Internal Medicine, vol. 243, no. 6, 1998, pp. 433-9.
Guru SC, Manickam P, Crabtree JS, et al. Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene. J Intern Med. 1998;243(6):433-9.
Guru, S. C., Manickam, P., Crabtree, J. S., Olufemi, S. E., Agarwal, S. K., & Debelenko, L. V. (1998). Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene. Journal of Internal Medicine, 243(6), 433-9.
Guru SC, et al. Identification and Characterization of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene. J Intern Med. 1998;243(6):433-9. PubMed PMID: 9681840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene. AU - Guru,S C, AU - Manickam,P, AU - Crabtree,J S, AU - Olufemi,S E, AU - Agarwal,S K, AU - Debelenko,L V, PY - 1998/7/29/pubmed PY - 1998/7/29/medline PY - 1998/7/29/entrez SP - 433 EP - 9 JF - Journal of internal medicine JO - J Intern Med VL - 243 IS - 6 N2 - For nearly a decade since the mapping of the multiple endocrine neoplasia type 1 (MEN1) locus to 11q13 and the suggestion that it is a tumour suppressor gene, efforts have been made to identify the gene responsible for this familial cancer syndrome. Recently, we have identified the MEN1 gene by the positional cloning approach. This effort involved construction of a 2.8-Mb physical map (D11S480-D11S913) based primarily on a bacterial clone contig. Using these resources, 20 new polymorphic markers were isolated which helped to reduce the interval for candidate genes by haplotype analysis in families and by loss of heterozygosity (LOH) studies in approximately 200 tumours, utilizing laser-assisted microdissection to obtain tumour cells with minimal or no admixture by normal cells. The interval was narrowed by LOH to only 300 kb, and nearly 20 new transcripts that map to this region of 11q13 were isolated and characterized. One of the transcripts was found by dideoxyfingerprinting and cycle sequencing to harbour deleterious germline mutations in affected individuals from MEN-1 kindreds and therefore identified as the MEN1 gene. The type of germline mutations and the identification of mutations in sporadic tumours support the Knudson's two-hit model of tumorigenesis for MEN-1. Efforts are being made to identify the function of the MEN1 gene-encoded protein, menin, and to study its role in tumorigenesis. SN - 0954-6820 UR - https://www.unboundmedicine.com/medline/citation/9681840/Identification_and_characterization_of_the_multiple_endocrine_neoplasia_type_1__MEN1__gene_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=1998&volume=243&issue=6&spage=433 DB - PRIME DP - Unbound Medicine ER -