Analysis of Somatic Variants in Growth Hormone Secreting Pituitary Adenomas by Whole Exome Sequencing | Biomedgrid

Background: Whole-genome and whole-exome sequencing (WES) studies of pituitary adenoma have reported on average three mutations per patient tumor and discovered calcium signaling pathway mediated role of tumorigenesis. The aim of this study is to analyze the somatic variants in growth hormone (GH) secreting pituitary adenoma using WES. Material and Methods: Whole-exome sequencing was used to identify somatic mutations in GH-secreting pituitary adenomas from 14 patients (7-45 years), including a sample from a patient with germline GPR101 duplication. A mean sequencing depth of 94x was achieved covering 98% of targeted exonic regions at a minimum depth of 10x. Results: A total of 30 somatic variants were identified from 14 tumor samples. A recurrent hotspot mutation in GNAS, a well-established gene implicated in acromegaly, were identified in four patients. In addition, missense variants in CACNA1H and WIPI1 were identified which have only been reported in single patients previously. We also observed variants in GNAQ, RASGEF1B and PARP4 (this latter one in the GPR101-positive sample) genes that are involved in cAMP and calcium signaling pathways but have not been previously reported to be altered in acromegaly. Large deletions in chromosomes 1, 6, 10, 11, 12, 16, 17, 19 and 20 were also observed in at least eight patients. Conclusion: By combining our findings with data from previous studies of GH-secreting adenomas, we conclude that pathways involving calcium and cAMP signaling are likely to be involved in the pathogenesis of somatotroph adenomas