Research Paper Volume 13, Issue 1 pp 1276—1293
Genomic and transcriptomic analysis of pituitary adenomas reveals the impacts of copy number variations on gene expression and clinical prognosis among prolactin-secreting subtype
- 1 Department of Cell Biology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
- 2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
- 3 Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
- 4 Department of Neurosurgery, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang 830001, China
- 5 China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
- 6 Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing 100070, China
Received: August 8, 2020 Accepted: September 29, 2020 Published: December 19, 2020
https://doi.org/10.18632/aging.202304How to Cite
Copyright: © 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Pituitary adenomas (PAs) are slow growing and benign primary intracranial tumors that often cause occupying effects or endocrine symptoms. PAs can be classified into various subtypes according to hormone secretion. Although widespread transcriptional alterations that cause aberrant hormone secretion have been characterized, the impact of genomic variations on transcriptional alterations is unclear due to the rare occurrence of single-nucleotide variations in PA. In this study, we performed whole-genome sequencing (WGS) on 76 PA samples across three clinical subtypes (PRL-PAs; GH-PAs, and NFPAs); transcriptome sequencing (RNA-seq) of 54 samples across these subtypes was also conducted. Nine normal pituitary tissues were used as controls. Common and subtype-specific transcriptional alterations in PAs were identified. Strikingly, widespread genomic copy number amplifications were discovered for PRL-PAs, which are causally involved in transcriptomic changes in this subtype. Moreover, we found that the high copy number variations (CNVs) in PRL-PA cause increased prolactin production, drug resistance and proliferative capacity, potentially through key genes with copy number amplification and transcriptional activation, such as BCAT1. This study provides insight into how genomic CNVs affect the transcriptome and clinical outcomes of PRL-PA and sheds light on the development of potential therapeutics for aberrantly activated targets.