SFEBES2013 Oral Communications Pituitary and neoplasia (8 abstracts)
Whole-exome sequencing studies of non-functioning pituitary adenomas
Paul Newey 1 , M Andrew Nesbit 1 , Andrew Rimmer 2 , Rosie Head 1 , Caroline Gorvin 1 , Moustafa Attar 3 , Lorna Gregory 3 , John Wass 4 , David Buck 3 , Niki Karavitaki 4 , Ashley Grossman 4 , Gilean McVean 2 , Olaf Ansorge 5 & Rajesh Thakker 1
1Academic Endocrine Unit, OCDEM, University of Oxford, Oxford, UK; 2Bioinformatics and Statistical Genetics Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; 3High-Throughput Genomics Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; 4Department of Endocrinology, OCDEM, Oxford University Hospitals Trust, Oxford, UK; 5Department of Neuropathology, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK.
Pituitary non-functioning adenomas (NFAs), arising mostly from gonadotroph cells, represent the second most common type of pituitary tumour, after prolactinomas. NFAs are monoclonal in origin, but mutations of genes associated with hereditary pituitary syndromes (e.g. MEN1, AIP, CDKN1B, and PRKAR1A), classic oncogenes or tumour suppressor genes are rarely found. We therefore performed whole-exome sequence analysis to determine the tumourigenic events in pituitary NFAs using DNA extracted from seven pituitary NFAs and matched leucocyte samples. Informed consent was obtained from individuals using protocols approved by local and national ethics committees. The seven patients (four males, three females) had a mean age of 55 years (range 39–82 years). Histologically, all tumours were confirmed as pituitary gonadotroph adenomas with no atypia and a Ki-67 index of ≤3%. Exome capture was performed using the SureSelect Human All Exon 50Mb Kit and sequencing undertaken using the Illumina HiSeq2000 platform. Somatic variants were identified and validated. A high degree of coverage was achieved such that ∼97% of targeted bases were represented by >10 bp reads. Twenty-four somatic variants were identified in the seven NFAs (mean =3.5 variants/tumour; range 1–7). The majority of variants occurred as missense single nucleotide variants (80%) with the remainder constituting synonymous changes or small frameshifting deletions. Each of the 24 mutations occurred in different genes, none of which had been previously reported to be associated with pituitary tumourigenesis. Three of the somatic mutations, occurring in independent tumours, represented putative driver genes involved in proliferation, apoptosis, and the cell-cycle check-point. However, analysis of these 3 genes in a validation set of 24 pituitary NFAs did not identify additional mutations. Thus, pituitary NFAs harbour few somatic mutations, consistent with their low proliferation rates and benign nature, but there appears to be no frequently mutated gene involved in the aetiology of pituitary NFAs.
Declaration of funding
This work was supported by funding from the Medical Research Council (grant numbers G9825289/2004, G1000467/2010 and 91070), the National Institute for Health Research (NIHR) and the Wellcome Trust (grant number 090532/Z/09/Z).
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more