Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene for multiple endocrine neoplasia type 1 (MEN1), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, we could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas.
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PMID:Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. 196 41

The recent chromosomal mapping of the genes for two different autosomal dominant inherited predispositions to multiple endocrine neoplasias promises to be a significant breakthrough for the understanding of the pathogenesis of such lesions. Multiple endocrine neoplasia type 1 (MEN1) associates primary hyperparathyroidism, lesions of the endocrine pancreas and pituitary adenomas. The first hint that the MEN1 gene is localized on chromosome 11 came from the finding of allele losses in MEN1 associated tumours. Subsequent genetic linkage analysis to restriction fragment length polymorphism (RFLP) markers assigned the gene to chromosome band 11q13. MEN2A is characterized by medullary thyroid carcinoma and phaeochromocytoma. The disease locus was localized to the centromeric region of chromosome 10 by genetic linkage. For both syndromes genetic linkage maps of the flanking regions have been established, and a set of RFLP markers is now available for premorbid identification of gene carriers in affected families. Analysis of allele losses showed that tumorigenesis of parathyroid and pancreatic lesions results from unmasking of a recessive mutation at the MEN1 locus, and by deletion mapping the tentative MEN1 region was restricted to a few million base pairs. In contrast, such losses appear to be relatively rare in MEN2A associated lesions.
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PMID:Multiple endocrine neoplasia. 198 11

Primary hyperparathyroidism is a common endocrine disease with a multifaceted genetic background, the elucidation of which has only begun. Among others, loss of the short arm of chromosome 1 and somatic inactivation of the multiple endocrine neoplasia type 1 gene (MEN1) in 11q13 represent significant alterations in the tumorigenesis. In the present study deletions of 1p were characterized and the findings were evaluated in relation to the loci of MEN1 and histone deacetylase 1 gene (HDAC1), a menin interacting partner in 1p, as well as to the clinical characteristics. Overall 1p LOH was detected in 18 of the 42 tumors analyzed (43%), and from the deletion patterns a main target interval of 40 cM was identified within 1p band 32.3-36.2. The mapping of HDAC1 centromeric of the main interval, and the lack of altered mRNA expression in tumors with LOH, suggest that HDAC1 is not the main target for 1p deletions in parathyroid tumors. Twenty-five of the 42 tumors (60%) showed alteration of either 1p, of the MEN1 locus, or both. Tumors with LOH at 11q13 had a significantly higher weight than tumors with 1p LOH. In conclusion, LOH in primary sporadic parathyroid adenomas occur frequently on the distal part of chromosome 1p and are thus clearly different from parathyroid carcinomas where the deletions are more proximally located. The findings support that the short arm of chromosome 1 harbors at least two different tumor suppressor genes involved in parathyroid tumorigenesis, the exact identification of which may provide a molecular basis for differential diagnosis of benign and malignant disease in the future.
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PMID:Distinct target regions for chromosome 1p deletions in parathyroid adenomas and carcinomas. 1223 10