Pituitary adenomas (PA) are benign tumors that develop in pituitary gland. Hormone secreting PA can cause overproduction of pituitary hormones leading to different systemic endocrine disorders (acromegaly, Cushings disease and others). Non-secreting PA can promote headaches (stretching of the dural sheath) and visual field defects (chiasma compression). We managed to obtain resected tumor samples from the patient having non-secreting PA, first tumor was resected in 2010, after operation patient had rapid regrowth and second resection was performed in 2012. Patient had two AIP gene variants rs641081 and rs4930199 in genomic DNA. Whole exome sequencing of both tumors and genomic DNA from white blood cells was carried out using single end sequencing in 3 batches on IonProton semiconductor sequencing system with average coverage 10x. Data analysis was performed using Galaxy main server (http://usegalaxy.org/). Variants were annotated using Annovar tool and obtained variants filtered. SNVs were filtered according to following parameters: sequencing depth >10, base Q at SNV position >13, non-synonymous SNV or stop-gain or stop-loss SNV, variation represented on both strands. Remaining SNV were manually inspected for irregularities using IGV. 9 non-synonymous SNVs were found in both tumors and not in genomic DNA, further 24 additional nonsynonymous SNVs were found in the second tumor that were not present in the first. The detected alterations include ALKBH8, ASB12, CST1, CLMN, PRSS41, ENPP1, E2F6 and SNVs in other genes, that are described to influence various cell functions, like regulation, signalling and cell cycle. All SNVs still to be validated by Sanger sequencing. Our findings indicate that second tumor had increased number of variations compared to first tumor, that could be caused by regrowth of second tumor from specific cell subpopulation from initial PA. Exome sequencing helps to discover genetic spectrum of known PA gene alterations and reveals new potential PA causative factors.
20 - 23 May 2017
European Society of Endocrinology