Phaeochromocytoma and Paraganglioma – Investigating the clinical utility of somatic sequencing in the management of sporadic phaeochromocytoma and paraganglioma

Lead applicant, Dr Ruth Casey is a Consultant Endocrinologist at Cambridge University Hospital NHS Foundation Trust and winner of AMEND’s 2018 Young Investigator Award. Dr Casey receives £10,000 from the 2019 AMEND Research Award.

Research summary: A phaeochromocytoma (PC) refers to a tumour located on the adrenal gland, which releases adrenaline and similar hormones. When a similar tumour occurs outside of the adrenal gland it is called a Paraganglioma (PGL) and can be located anywhere from the skill to the pelvis. Though PC and PGL are relatively rare tumours, they are important because, a) they can affect young patients, and b) these tumours have the potential to behave in a malignant or cancerous manner and unfortunately, at present, there are few treatment options for patients who develop metastatic disease. New and more effective biomarkers are required to predict those patients at risk of developing metastatic disease and to inform current long-term surveillance strategies.

We now understand that a large proportion of PC and PGL are hereditary (40%) and recognising the hereditary basis of these tumours has enabled us to better manage patients with these tumours, and to predict their malignant potential. However, the majority of studies would suggest that in a proportion (~30%) of these individuals, a non-hereditary genetic alteration can be identified in their PC or PGL to account for the development of that tumour. This type of non-hereditary genetic alteration is called a ‘driver somatic mutation’ and identifying these mutations can help i) predict the malignant potential of the tumour, ii) may help identify suitable treatment options for the patient if metastatic disease develops, and iii) can help to relieve anxiety in the family regarding a potential familial risk of developing these tumours. At present, testing for a somatic driver mutation in PC and PGL is not performed routinely in clinical practice in the United Kingdom. The aim of this study is to investigate the clinical utility of somatic mutation testing in PC and PGL in order to better understand the potential benefits of translating this type of testing into routine clinical practice.

SDH Syndromes – Is there a genotype-phenotype correlation in SDHB that can guide surveillance screening?

Dr Scott Akker, Consultant Endocrinologist from St Bartholomew’s Hospital in London receives a small grant of £1,000 towards this project.

Research Summary: We would like to investigate whether certain ‘types’ of SDHB gene changes make it more likely that a person will develop a phaeochromocytoma/paraganglioma (PCC/PGL); and also whether these are more likely to spread. We propose to gather scans and gene test results from 500 SDHB patients and their families from all round the UK, analyse the scans closely and calculate whether there is a link between certain gene changes and the likelihood of forming a PCC/PGL. This will help us to target NHS resources better and to improve clinical care for those most at risk.