Molecular genetic studies of sporadic pituitary tumors

Journal Article · Tue Feb 01 04:00:00 EST 1994 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.78.2.387· OSTI ID:54495

Boggild, M D; Jenkinson, S; McTernan, P; Perrett, C W; Clayton, R N ^[1]; Thakker, R V ^[2]; Pistorello, M; Boscaro, M; Scanarini, M ^[3]

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1. Keele Univ., Stoke-on-Trent (United Kingdom)
2. Hammersmith Hospital, London (United Kingdom)
3. Univ. of Padua (Italy)

Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor 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 rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of G{sub s{alpha}} were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of G{sub s{alpha}} were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of G{sub s{alpha}} are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype. 30 refs., 3 figs., 1 tab.

• OSTI ID: 54495
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 2 Vol. 78; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
GENE AMPLIFICATION
GENE MUTATIONS
GENETIC MAPPING
HUMAN CHROMOSOME 1
HUMAN CHROMOSOME 13
HUMAN CHROMOSOME 17
HUMAN CHROMOSOME 22
HUMAN CHROMOSOME 5
HUMAN CHROMOSOMES
NEOPLASMS
ONCOGENES
PITUITARY GLAND