Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of heterozygosity for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumours from subjects with MEN-1 has been well documented and has led to the hypothesis that the MEN-1 gene functions as a recessive tumour suppressor gene. We report a case of MEN-1 with duodeno-pancreatic gastrinoma, parathyroid hyperplasia, pituitary adenoma, adrenal adenoma, and lipomas, whose rare association with a malignant gastrointestinal stromal tumour (GIST) represents an undescribed combination. MEN-1 mutation in this family was shown as a frameshift (1607delA) in exon 10. To assess the role of the MEN-1 gene in the pathogenesis of tumours less commonly associated with MEN-1, we studied GIST DNA for loss of the unaffected MEN-1 gene allele. Stromal tumour and peripheral leucocyte DNAs from our patient were examined for loss of heterozygosity using the PYGM microsatellite polymorphism and an intragenic polymorphism (D418D in exon 9) in the MEN-1 gene. We showed no evidence for loss of the wild-type MEN-1 allele in GIST. The MEN-1 germline inactivating mutation 1607delA-ter558 in exon 10 was detected in the stromal tumour DNA, but no somatic mutation in the wild-type MEN-1 allele in GIST DNA was detected. Occurrence of GIST could be consistent with the possibility that this MEN-1-related uncommon neoplasm arose independently by a mechanism unrelated to the MEN-1 gene.
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PMID:A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type 1. 1124 25

Adrenal masses are a common problem affecting 3-7% of the population. The majority turn out to be benign adrenocortical adenomas, which may be functional or non-functional. Much more rarely, these masses represent a primary adrenal carcinoma. It is becoming increasingly recognized that of the benign functioning adenomas or hyperplasias, the majority will hypersecrete aldosterone and this will be more frequently detected when hypertensive populations are screened for this disease. In contrast, the incidence of primary adrenocortical carcinoma has remained steady and for this disease, surgery represents the mainstay of treatment. The advent of laparoscopic adrenal surgery has lowered the threshold size for recommending surgery for asymptomatic adrenal masses and as such, an increased proportion of adrenocortical cancers are being resected and detected at an earlier stage. Recent progress has been made in our understanding of the key genetic changes which underpin the biology of this disease. Progression from adrenal adenoma to carcinoma involves a monoclonal proliferation of cells which, among other defects, have undergone chromosomal duplication at the 11p15.5 locus leading to overexpression of the IGF2 gene and abrogation of expression of the CDKN1C and H19 genes. TP53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored. Other key oncogenes and tumour suppressor genes remain to be identified although the chromosomal loci in which they lie can be identified at 17p, 1p, 2p16 and 11q13 for tumour suppressor genes and chromosomes 4, 5 and 12 for oncogenes.
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PMID:Clinical and molecular aspects of adrenocortical tumourigenesis. 1295 90