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Abstract

Pituitary adenomas most commonly are identified as small, incidental microadenomas. They however may progress to macroadenoma forming intra and later suprasellar tumors which in about 1/3 of cases invade surrounding structures at the time of diagnosis. Mechanism of pituitary tumorigenesis remains still elusive. Because the value of karyotyping is limited by the technical problems related to cytogenetic methods, we studied the spectrum of chromosomal imbalances associated with pituitary adenoma using comparative genomic hybridization (CGH). Copy number aberrations on all 22 autosomes were evaluated by CGH using advanced computer software. In total, fifteen patients were included in the study of 9 non-invasive, 4 invasive and two recurrent adenomas. The mean age of the patients were 48 years ranging from 36 to 68 years. Five tumors showed hormonal activity. The histogram of all 15 cases representing the DNA imbalances as an incidence curve along each chromosome showed losses particularly for chromosomes 1p, 2q, 4, 5, 6, 11q, 12q, 13q and 18q as well as overrepresentation on 9q, 16p, 17p, 19, 20q. Functioning adenomas carried more imbalances than non-functioning, specifically deletions on chromosome 4 and 18q as well as overrepresentations of chromosomes 17 and 19. Invasive adenomas carried more overrepresentations at 1p34 than non-invasive tumors. Recurrent adenomas harbored more alterations than primary tumors, particularly DNA gains. The primary data is accessible at our CGH online tumor database at http://amba.charite.de/cgh. Reviewing the existing literature on the genetics of pituitary adenoma and discussing our results in this context, we hope that our study will contribute to the knowledge of this neoplasm.

Landscape of Genomic Alterations in Pituitary Adenomas

“…Classical cytogenetic studies have demonstrated differences in degree of chromosomal alterations among pituitary adenomas, but the results are inconsistent (55, 56). …”

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas

“…Furthermore, increased expression of the pituitary tumor-transforming gene (PTTG), the index mammalian securin that enables faithful chromatid separation during mitosis (15)(16)(17), was also associated with aneuploidy in these adenomas (16). Loss of heterozygosity (18) and somatic copy number alterations (SCNAs) were reported in secreting and more aggressively growing sporadic pituitary adenomas (18)(19)(20)(21)(22). De novo SCNAs, commonly seen in tumors, may arise as a consequence of DNA damage and genome instability and can result in cell dysfunction (23,24).…”

MANAGEMENT OF ENDOCRINE DISEASE: Clinicopathological classification and molecular markers of pituitary tumours for personalized therapeutic strategies

“…Bates et al (88) studied loss of heterozygosity (LOH) associated with an aggressive behaviour and identified a significantly higher frequency of LOH in invasive tumours compared with non-invasive tumours and demonstrated that allelic deletion in the invasive tumours is clustered at four loci: 11q13 (multiple endocrine neoplasm type 1 (MEN1) and aryl hydrocarbon receptor-interacting protein (AIP)), 13q12-14, 10q26 and 1p. The frequency of these alterations has been confirmed in other publications (58,89,90,91,92,93,94). To identify the specific alterations associated with tumour behaviour and evaluate the impact of genomic alteration on transcriptomic activity, we recently conducted an integrated genomic profiling study of PRL tumours classified according to our pathological classification (58).…”