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Screening of the Men1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors.
Cancer Res. 2000 Oct 01; 60(19):5553-7.CR

Abstract

Hyperparathyroidism is the first manifestation in a majority of multiple endocrine neoplasia (MEN1) patients. To discriminate between sporadic and hereditary parathyroid tumors and characterize MEN1 somatic mutations, we examined MEN1 gene mutations in patients who had undergone surgery for sporadic parathyroid tumors. DNA was extracted from fresh frozen parathyroid tumor specimens from 112 patients as well as from peripheral blood leukocytes from 64 of the 112 patients. Sequence analysis was performed to examine exons 2-10 of the MEN1 gene for mutations. Loss of heterozygosity (LOH) was also examined by an analysis of codon 418 and 541, which lie within a polymorphic region of MEN1. Somatic MEN1 mutations were found in 25 of the 112 patients (22%). Two patients had two point mutations (508del33 and Y341X and 363insT and 1767delT, respectively). A total of 27 mutations were characterized, 20 of which have not been reported previously. There were 7 nonsense mutations, 10 frameshift mutations, 2 splice site deletions, 5 missense mutations, and 3 in-frame mutations. Nineteen mutations (70%) predicted truncation of the menin protein. Germ-line MEN1 mutations were found in 3 of 64 patients (5%) who had no family history of endocrine tumors associated with MEN1, and these patients were identified as MEN1 gene probands. LOH at the MEN1 locus was detected in three parathyroid tumors showing germ-line mutation. LOH was significantly frequent in parathyroid tumors with somatic MEN1 mutations (15 of 22 tumors, 68%) but not in those without germ-line or somatic MEN1 mutations (14 of 51 tumors, 28%; P = 0.0011). Our findings suggest that alterations of both alleles of the MEN1 gene may be associated not only with endocrine tumors of affected MEN1 patients but also with sporadic parathyroid tumors. Germ-line MEN1 gene analysis can distinguish heritable from nonheritable parathyroid tumors, and MEN1 gene evaluation of patients with apparently sporadic parathyroid tumor is recommended before parathyroid surgery.

Authors+Show Affiliations

Noguchi Thyroid Clinic and Hospital Foundation, Oita, Japan. uchino@noguchi-med.or.jpNo 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

Language

eng

PubMed ID

11034102

Citation

Uchino, S, et al. "Screening of the Men1 Gene and Discovery of Germ-line and Somatic Mutations in Apparently Sporadic Parathyroid Tumors." Cancer Research, vol. 60, no. 19, 2000, pp. 5553-7.
Uchino S, Noguchi S, Sato M, et al. Screening of the Men1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors. Cancer Res. 2000;60(19):5553-7.
Uchino, S., Noguchi, S., Sato, M., Yamashita, H., Yamashita, H., Watanabe, S., Murakami, T., Toda, M., Ohshima, A., Futata, T., Mizukoshi, T., Koike, E., Takatsu, K., Terao, K., Wakiya, S., Nagatomo, M., & Adachi, M. (2000). Screening of the Men1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors. Cancer Research, 60(19), 5553-7.
Uchino S, et al. Screening of the Men1 Gene and Discovery of Germ-line and Somatic Mutations in Apparently Sporadic Parathyroid Tumors. Cancer Res. 2000 Oct 1;60(19):5553-7. PubMed PMID: 11034102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening of the Men1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors. AU - Uchino,S, AU - Noguchi,S, AU - Sato,M, AU - Yamashita,H, AU - Yamashita,H, AU - Watanabe,S, AU - Murakami,T, AU - Toda,M, AU - Ohshima,A, AU - Futata,T, AU - Mizukoshi,T, AU - Koike,E, AU - Takatsu,K, AU - Terao,K, AU - Wakiya,S, AU - Nagatomo,M, AU - Adachi,M, PY - 2000/10/18/pubmed PY - 2001/2/28/medline PY - 2000/10/18/entrez SP - 5553 EP - 7 JF - Cancer research JO - Cancer Res. VL - 60 IS - 19 N2 - Hyperparathyroidism is the first manifestation in a majority of multiple endocrine neoplasia (MEN1) patients. To discriminate between sporadic and hereditary parathyroid tumors and characterize MEN1 somatic mutations, we examined MEN1 gene mutations in patients who had undergone surgery for sporadic parathyroid tumors. DNA was extracted from fresh frozen parathyroid tumor specimens from 112 patients as well as from peripheral blood leukocytes from 64 of the 112 patients. Sequence analysis was performed to examine exons 2-10 of the MEN1 gene for mutations. Loss of heterozygosity (LOH) was also examined by an analysis of codon 418 and 541, which lie within a polymorphic region of MEN1. Somatic MEN1 mutations were found in 25 of the 112 patients (22%). Two patients had two point mutations (508del33 and Y341X and 363insT and 1767delT, respectively). A total of 27 mutations were characterized, 20 of which have not been reported previously. There were 7 nonsense mutations, 10 frameshift mutations, 2 splice site deletions, 5 missense mutations, and 3 in-frame mutations. Nineteen mutations (70%) predicted truncation of the menin protein. Germ-line MEN1 mutations were found in 3 of 64 patients (5%) who had no family history of endocrine tumors associated with MEN1, and these patients were identified as MEN1 gene probands. LOH at the MEN1 locus was detected in three parathyroid tumors showing germ-line mutation. LOH was significantly frequent in parathyroid tumors with somatic MEN1 mutations (15 of 22 tumors, 68%) but not in those without germ-line or somatic MEN1 mutations (14 of 51 tumors, 28%; P = 0.0011). Our findings suggest that alterations of both alleles of the MEN1 gene may be associated not only with endocrine tumors of affected MEN1 patients but also with sporadic parathyroid tumors. Germ-line MEN1 gene analysis can distinguish heritable from nonheritable parathyroid tumors, and MEN1 gene evaluation of patients with apparently sporadic parathyroid tumor is recommended before parathyroid surgery. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11034102/Screening_of_the_Men1_gene_and_discovery_of_germ_line_and_somatic_mutations_in_apparently_sporadic_parathyroid_tumors_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11034102 DB - PRIME DP - Unbound Medicine ER -