SDHB and its role in epigenetic alteration in malignant phaeochromocytoma

A phaeochromocytoma (PC) refers to a tumour located on the adrenal gland, which releases adrenaline and similar hormones and causes high blood pressure (in severe cases this may be fatal). When a similar tumour occurs outside of the adrenal gland it is called a paraganglioma (PGL) and can be located anywhere from skull to pelvis. Though PC and PGL are relatively rare tumours they are important because (a) they are frequently unrecognised or only diagnosed after undue delay but if diagnosed early they can usually be successfully treated and morbidity reduced, (b) a high proportion of cases are caused by inherited gene mutations, particularly in the genes encoding the succinate dehydrogenase complex. Diagnosis of these inherited cases is important because at risk relatives can be tested to see whether they will develop a tumour and there is known to be a high risk of malignant tumours with gene mutations. However, in patients who carry a gene mutation and develop a tumour it is difficult to predict malignancy and vigilant clinical, radiological and biochemical surveillanc is required. Furthermore current treatment strategies of malignant tumours have limited success and cure is not currently achievable. New therapies are urgently required and recent work suggests that changes in DNA methylation are a common feature of related tumours and that it might be possible to exploit this to develop new therapies. Thus we plan to investigate DNA methylation changes in related tumours to understand if this methylation change can be adopted as a screening method to allow early detection of malignant disease and secondly whether this epigenetic alteration can be modified to offer new more effective treatment strategies.


Award Date
26 May 2016
Award Value
Principal Investigator
Professor Ruth Casey
Host Institution
National University of Ireland, Galway
Research Training Fellowships for Healthcare Professionals