TERT structural rearrangements in metastatic pheochromocytomas
- Author(s)
- Dwight, T; Flynn, A; Amarasinghe, K; Benn, DE; Lupat, R; Li, J; Cameron, D; Hogg, A; Balachander, S; Candiloro, IL; Wong, S; Robinson, BG; Papenfuss, AT; Gill, AJ; Dobrovic, A; Hicks, RJ; Clifton-Bligh, R; Tothill, RW;
- Journal Title
- Endocrine Related Cancer
- Publication Type
- Journal Article in press
- Abstract
- Pheochromocytomas (PC) and paragangliomas (PGL) are endocrine tumors for which the genetic and clinico-pathological features of metastatic progression remain incompletely understood. As a result, the risk of metastasis from a primary tumor cannot be predicted. Early diagnosis of individuals at high risk of developing metastases is clinically important and the identification of new biomarkers that are predictive of metastatic potential is of high value. Activation of TERT has been associated with a number of malignant tumors, including PC/PGL. However, the mechanism of TERT activation in the majority of PC/PGL remains unclear. As TERT promoter mutations occur rarely in PC/PGL, we hypothesized that other mechanisms - such as structural variations - may underlie TERT activation in these tumors. From 35 PC and four PGL, we identified three primary PC that developed metastases with elevated TERT expression, each of which lacked TERT promoter mutations and promoter DNA methylation. Using whole genome sequencing we identified somatic structural alterations proximal to the TERT locus in two of these tumors. In both tumors, the genomic rearrangements led to positioning of super-enhancers proximal to the TERT promoter, that are likely responsible for activation of the normally tightly repressed TERT expression in chromaffin cells.
- Publisher
- Bioscientifica
- Research Division(s)
- Bioinformatics
- PubMed ID
- 28974544
- Publisher's Version
- https://doi.org/10.1530/ERC-17-0306
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-10-16 01:59:54
Last Modified: 2017-10-16 02:37:07