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Somatic mutation of the MEN1 gene in parathyroid tumours.
Nat Genet. 1997 Aug; 16(4):375-8.NGen

Abstract

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

Authors+Show Affiliations

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

9241276

Citation

Heppner, C, et al. "Somatic Mutation of the MEN1 Gene in Parathyroid Tumours." Nature Genetics, vol. 16, no. 4, 1997, pp. 375-8.
Heppner C, Kester MB, Agarwal SK, et al. Somatic mutation of the MEN1 gene in parathyroid tumours. Nat Genet. 1997;16(4):375-8.
Heppner, C., Kester, M. B., Agarwal, S. K., Debelenko, L. V., Emmert-Buck, M. R., Guru, S. C., Manickam, P., Olufemi, S. E., Skarulis, M. C., Doppman, J. L., Alexander, R. H., Kim, Y. S., Saggar, S. K., Lubensky, I. A., Zhuang, Z., Liotta, L. A., Chandrasekharappa, S. C., Collins, F. S., Spiegel, A. M., ... Marx, S. J. (1997). Somatic mutation of the MEN1 gene in parathyroid tumours. Nature Genetics, 16(4), 375-8.
Heppner C, et al. Somatic Mutation of the MEN1 Gene in Parathyroid Tumours. Nat Genet. 1997;16(4):375-8. PubMed PMID: 9241276.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Somatic mutation of the MEN1 gene in parathyroid tumours. AU - Heppner,C, AU - Kester,M B, AU - Agarwal,S K, AU - Debelenko,L V, AU - Emmert-Buck,M R, AU - Guru,S C, AU - Manickam,P, AU - Olufemi,S E, AU - Skarulis,M C, AU - Doppman,J L, AU - Alexander,R H, AU - Kim,Y S, AU - Saggar,S K, AU - Lubensky,I A, AU - Zhuang,Z, AU - Liotta,L A, AU - Chandrasekharappa,S C, AU - Collins,F S, AU - Spiegel,A M, AU - Burns,A L, AU - Marx,S J, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 375 EP - 8 JF - Nature genetics JO - Nat. Genet. VL - 16 IS - 4 N2 - Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome. SN - 1061-4036 UR - https://www.unboundmedicine.com/medline/citation/9241276/Somatic_mutation_of_the_MEN1_gene_in_parathyroid_tumours_ L2 - http://dx.doi.org/10.1038/ng0897-375 DB - PRIME DP - Unbound Medicine ER -