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7 May 2018 at 12:00AM

Australian Research led by Trisha Dwight

We are so pleased to see recently published Australian research, led by Trisha Dwight and including a team from Peter MacCallum, Sydney University, Kolling Institute and more, looking at the role of TERT in metastatic Pheochromocytomas (PC) and Paraganglioma (PGL). A team from Denmark is also seen on the author list showing great global collaboration.

A TERT gene provides instruction for making one component of an enzyme called teleomerase, teleomerase is abnormally active in most cancer cells which divide and grow without control or order.

Here is more from Trisha as quoted from the Autumn issue of the Kolling Institute newsletter….

Patient donated tumours are invaluable for understanding the mechanisms of cancer.

Our group has been studying specific adrenal tumours, known as phaeochromocytomas and paragangliomas. Although these tumours are rare, they are associated with a high level of disease and poor quality of life. Cells from these tumours are capable of spreading (metastasising) to other sites, such as bone, lungs, lymph nodes and liver. As there are currently no highly effective treatments for individuals who develop metastatic disease, their long term survival is limited (with only one in every two patients surviving beyond five years).

Our current understanding of how and why these tumour cells spread to other sites is limited, which means it is extremely difficult to predict if, or even when, metastatic disease is likely to occur in any individual who develops these tumours. This causes considerable anxiety for both patients and their families, watching and waiting for metastatic disease that may never develop. It also makes clinical management extremely difficult and lifelong surveillance, by way of biochemical testing and imaging, is required. The identification of early markers of metastatic potential is a high priority.

One area of our research focuses on identifying genetic abnormalities that are unique to metastatic tumours. Recently our studies have focused on TERT, a gene which is normally expressed at very low levels in adult tissues. However, recent studies have shown that high levels of TERT have been observed in a number of cancer types, including phaeochromocytomas and paragangliomas where approximately 25% exhibit abnormally high levels of TERT. The mechanism leading to TERT overexpression in phaeochromocytomas and paragangliomas remains unclear. Our study was able to uncover, for the first time in this tumour type, one of the mechanisms responsible for TERT overexpression in a portion of metastatic phaeochromocytomas. Through the use of a method known as “whole genome sequencing”, we identified chromosomal rearrangements that are responsible for TERT overexpression in a group of metastatic phaeochromocytomas. These chromosomal rearrangements resulted in the placement of enhancer regions (that are capable of activating genes) near the TERT gene, resulting in TERT overexpression.

We hope our findings, combined with further studies, will lead to the identification of effective treatments that ultimately halt the spread of disease in individuals with phaeochromocytoma and paraganglioma.

To read the full Kolling Institute Autumn newsletter, click here

To read the scientific abstract published by Dr Trisha Dwight and team, click here

Category: Research