Endocrine Abstracts (2002) 3 P141

Hunting for oncogenes in pituitary adenomas - a cautionary tale of new technology

D Morris1, D Lillington2, J Strefford2, M Korbonits1, B Young2 & AB Grossman1

1Department of Endocrinology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London , UK; 2ICRF Department of Medical Oncology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.

The proto-oncogene Gsalpha has been implicated in a significant minority of somatotrophinomas, but the search for candidate oncogenes in the remaining somatotrophinomas, and in the great majority of other types of benign pituitary adenomas, has so far been unsuccessful. Microarray-based comparative genomic hybridisation (microarray-CGH) is a novel DNA microarray technique that has been shown to identify gain or loss at the gene level, and has been proposed as a tool to screen for candidate oncogenes in tumours. We have therefore explored the use of CGH-microarray chips (AmpliOnc v7, Vysis, UK) containing 59 clones from 57 oncogenes commonly amplified in human tumours to study DNA from 13 pituitary tumours (4 non-functioning; 3 corticotrophs; 3 somatotrophs; 2 lactotrophs; 1 FSHoma), and one normal pituitary specimen. Conventional CGH was also performed on the same 13 tumours. In both techniques, tumour DNA and normal control DNA were labelled by nick translation with green- and red-fluorescence tagged nucleotides respectively. Labelled tumour and control DNA were combined and hybridised to normal metaphase chromosomes (CGH) and oncogene targets (microarray-CGH). Microarray-CGH revealed 192 apparent gains covering 48 oncogenes in the 13 tumours. The most frequent genetic gain observed was MYCL1 in 9 of 13 tumours (69%). Particularly high levels of gain were obtained in certain tumours for the genes CTSB, YES1, GLI and RAF1. However, we were unable to corroborate these oncogenic gains by real-time PCR. Similarly, there was poor concordance between the oncogenic gain seen by microarray-CGH and the regional chromosomal abnormalities seen in 9 of the 13 tumours by conventional CGH. It therefore appears that the technique of AmpliOnc microarray-CGH, in its current form, may spuriously suggest specific oncogenic amplifications, and thus considerable care must be taken to validate such novel technologies.

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