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Title: Molecular screening of pituitary adenomas for gene mutations and rearrangements

Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus onmore » chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.« less
Authors:
; ; ;  [1]
  1. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))
Publication Date:
OSTI Identifier:
5412165
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Clinical Endocrinology and Metabolism; (United States); Journal Volume: 77:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HUMAN CHROMOSOMES; GENE MUTATIONS; PITUITARY GLAND; ADENOMAS; ACROMEGALY; GROWTH FACTORS; BODY; CARCINOMAS; CHROMOSOMES; DISEASES; ENDOCRINE DISEASES; ENDOCRINE GLANDS; GLANDS; MITOGENS; MUTATIONS; NEOPLASMS; ORGANIC COMPOUNDS; ORGANS; PROTEINS 550400* -- Genetics