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Molecular genetic studies of sporadic pituitary adenomas.

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thesis
posted on 19.11.2015, 08:50 by Michael Derek. Boggild
Tumour formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumour suppressor genes. The role of such mutations in the development of pituitary tumours has been studied. Tumours from 88 patients, representing the 4 major classes of pituitary adenoma, were investigated. In DNA extracted from matched leucocyte and tumour samples allelic deletions were sought with 15 probes identifying restriction fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20 and 22. Evidence of amplification or re-arrangement of 10 recognised cellular oncogenes (NRAS, MYCL1, MYCN, MYC, HRAS, BCL1, HSTF1, SEA, KRAS2 and FOS) was sought in tumour DNA. Activating dominant mutations of the oncogene Gsalpha were detected using the polymerase chain reaction to amplify exons 7-10 and hybridising the product to normal and mutant allele specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumours (18%) representing all 4 major sub-types. Deletions on other autosomes were observed in less than 6% of tumours. Three adenomas had deletions on multiple autosomes, two of these were aggressive and recurrent. Mutations of Gsalpha were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumours in this series. No evidence of amplification or rearrangement of other recognised cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the 4 major types of pituitary adenoma whilst activating mutations of Gsalpha are confirmed to be specific to somatotrophinomas. Two aggressive tumours were found to have multiple autosomal losses, suggesting a multi-step progression in the development of tumours of this phenotype.

History

Date of award

01/01/1995

Author affiliation

College of Medicine, Biological Sciences and Psychology

Awarding institution

University of Leicester

Qualification level

Doctoral

Qualification name

MD

Language

en

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