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Multiple endocrine neoplasia type 1 (MEN1): LOH studies in a affected family and in sporadic cases.
Anticancer Res. 1998 Jul-Aug; 18(4A):2685-9.AR

Abstract

Multiple endocrine neoplasia (Menl) is an autosomai dominant hereditary trait characterized by tumors of endocrine tissues. The MEN1 gene maps to chromosome llql3, has been recently isolated, and encodes a protein termed menin that is ubiquitously expressed. This gene is likely to be a tumor suppressor gene, with tumors developing after the inactivation of both copies of the gene in a single cell. In agreement with this, 11q-deletions (loss of heterozygosity) are frequently found in neoplasms from MEN1 patients. In this study, DNA from family-members was extracted and analysed for 10 microsatellites flanking the MEN1-gene on chromosome 11q. SSCP was used to determine the presence of MEN1-mutations in several patients. DNA was extracted from paraffin blocks containing tissue from 10 parathyroid tumors (4 familial and 6 sporadic) and 2 gastrinomas (both from patients of the Men1-family). LOH was determined by comparing the autoradiographic patterns of several markers between the normal tissue and the malignant tissue counterpart. All the affected individuals in the MEN1-family shared one haplotype, not present in the healthy individuals. We searched for mutations at the MEN1 gene (SSCP-analysis) in several affected members. An SSCP-mobility shift was found at exon 9, and direct sequencing showed that this corresponded to a common polymorphism at codon 418 (GAC/GAT), LOH, a genetic alteration characteristic of genomic regions containing tumor suppressor genes, was found in all the parathyroid tumors, but not in two gastrinomas. SSCP-analysis of the MEN1-exon 9 polymorphism showed that LOH included the MEN1-gene in the informative parathyroid tumors. In conclusion, LOH at 11q is frequent in Menl-parathyroid tumors, either sporadic or familial, and the deletion involves the MEN1-gene. In contrast, the two gastrinomas did not show LOH, indicating the existence of a second mutation other than the MEN1-deletion in these tumors. Our data suggest that the mechanism that drives tumorigenesis in Menl either familial or sporadic, is influenced by the tissue context.

Authors+Show Affiliations

Servicio de Endocrinologia, Hospital, Central de Asturias, Oviedo, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9703929

Citation

Valdes, N, et al. "Multiple Endocrine Neoplasia Type 1 (MEN1): LOH Studies in a Affected Family and in Sporadic Cases." Anticancer Research, vol. 18, no. 4A, 1998, pp. 2685-9.
Valdes N, Alvarez V, Diaz-Cadorniga F, et al. Multiple endocrine neoplasia type 1 (MEN1): LOH studies in a affected family and in sporadic cases. Anticancer Res. 1998;18(4A):2685-9.
Valdes, N., Alvarez, V., Diaz-Cadorniga, F., Aller, J., Villazon, F., Garcia, I., Herrero, A., & Coto, E. (1998). Multiple endocrine neoplasia type 1 (MEN1): LOH studies in a affected family and in sporadic cases. Anticancer Research, 18(4A), 2685-9.
Valdes N, et al. Multiple Endocrine Neoplasia Type 1 (MEN1): LOH Studies in a Affected Family and in Sporadic Cases. Anticancer Res. 1998 Jul-Aug;18(4A):2685-9. PubMed PMID: 9703929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple endocrine neoplasia type 1 (MEN1): LOH studies in a affected family and in sporadic cases. AU - Valdes,N, AU - Alvarez,V, AU - Diaz-Cadorniga,F, AU - Aller,J, AU - Villazon,F, AU - Garcia,I, AU - Herrero,A, AU - Coto,E, PY - 1998/8/15/pubmed PY - 1998/8/15/medline PY - 1998/8/15/entrez SP - 2685 EP - 9 JF - Anticancer research JO - Anticancer Res. VL - 18 IS - 4A N2 - Multiple endocrine neoplasia (Menl) is an autosomai dominant hereditary trait characterized by tumors of endocrine tissues. The MEN1 gene maps to chromosome llql3, has been recently isolated, and encodes a protein termed menin that is ubiquitously expressed. This gene is likely to be a tumor suppressor gene, with tumors developing after the inactivation of both copies of the gene in a single cell. In agreement with this, 11q-deletions (loss of heterozygosity) are frequently found in neoplasms from MEN1 patients. In this study, DNA from family-members was extracted and analysed for 10 microsatellites flanking the MEN1-gene on chromosome 11q. SSCP was used to determine the presence of MEN1-mutations in several patients. DNA was extracted from paraffin blocks containing tissue from 10 parathyroid tumors (4 familial and 6 sporadic) and 2 gastrinomas (both from patients of the Men1-family). LOH was determined by comparing the autoradiographic patterns of several markers between the normal tissue and the malignant tissue counterpart. All the affected individuals in the MEN1-family shared one haplotype, not present in the healthy individuals. We searched for mutations at the MEN1 gene (SSCP-analysis) in several affected members. An SSCP-mobility shift was found at exon 9, and direct sequencing showed that this corresponded to a common polymorphism at codon 418 (GAC/GAT), LOH, a genetic alteration characteristic of genomic regions containing tumor suppressor genes, was found in all the parathyroid tumors, but not in two gastrinomas. SSCP-analysis of the MEN1-exon 9 polymorphism showed that LOH included the MEN1-gene in the informative parathyroid tumors. In conclusion, LOH at 11q is frequent in Menl-parathyroid tumors, either sporadic or familial, and the deletion involves the MEN1-gene. In contrast, the two gastrinomas did not show LOH, indicating the existence of a second mutation other than the MEN1-deletion in these tumors. Our data suggest that the mechanism that drives tumorigenesis in Menl either familial or sporadic, is influenced by the tissue context. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/9703929/Multiple_endocrine_neoplasia_type_1__MEN1_:_LOH_studies_in_a_affected_family_and_in_sporadic_cases_ L2 - http://www.diseaseinfosearch.org/result/4954 DB - PRIME DP - Unbound Medicine ER -