A5 SDHB Genomics Study

• 
  Head of Laboratory
  Dr Richard Tothill

  rtothill@unimelb.edu.au

  View researcher's webpage

Project Details

Phaeochromocytomas (PC) (originating from Greek, meaning dusky-coloured tumour) and paragangliomas (PGL) originate from endocrine cells found in the adrenal gland (PC) or paraganglia proximal to sympathetic and parasympathetic nerve tissues near the spine, neck or other organs such as the bladder and prostate.

PC and PGL are some of the most heritable neoplasms with approximately 30-40 per cent of PC/PGL patients carrying disease-causing mutations that predispose to disease often at a young age. PC/PGL often present with symptoms relating to excessive production of the fight or flight hormones (adrenaline or noradrenaline) including hypertension, rapid or irregular heartbeat, sweating and anxiety.

Approximately 10-20 per cent of PC/PGL become metastatic, where the cancer cells spread to other parts of the body. There are currently limited treatment options for those patients with metastatic PC/PGL. Furthermore, there are no recognised tests that can predict who may be at higher risk. Patients developing PC/PGL by inheritance of a mutation in the gene SDHB are known to be more likely to develop metastases, although the exact reason why only some tumours become aggressive and spread is unknown.

We are using genomics to understand the pathogenesis of metastatic PPGL in SDHB mutation carriers, identify biomarkers of metastatic risk to inform optimal surveillance strategies and find new therapeutic targets for patient treatment.

Researchers

Dr Richard Tothill – Genomics Group Leader
Ms Shiva Balanchander – Research Assistant
Dr Andrew Pattison – Research Officer (Bioinformatics)

Collaborators

Australia

Peter MacCallum Cancer Centre, Melbourne
Kolling Institute, Sydney
Royal North Shore Hospital, Sydney

International

National Institute of Health, USA
University of Texas, USA
University of Colorado, USA
Uppsala University, Sweden
Tufts Medical Centre, Boston, USA
University of Florida, USA
University of Auckland, New Zealand
University of Michigan, USA
National Cancer Centre Singapore (NCCS), Singapore

Funding

NHMRC

Pheo Para Alliance

Paradifference

Research Publications

1. Dwight, T., Flynn, A., Amarasinghe, K., Benn, D.E. Lupat, R., Li, J.,…Tothill, R.W. TERT Structural rearrangements in metastatic pheochromocytomas. Endocrine-Related Cancer. 2018.25(1):1-9.

2. Flynn,A, Dwight, T, Benn, D, Deb, S, Colebatch, AJ, Fox, S… Tothill, R.W Cousins not twins: intra and inter-tumoral heterogeneity in syndromic neuroendocrine tumours. Journal of Pathology. 2017 242(3):273-283

3. Flynn A, Dwight T, Harris J, Benn D, Zhou L, Hogg A, Catchpoole, D, … Tothill, RW Pheo-type: a diagnostic gene-expression assay for the classification of pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2016. 101(3): 1034-43.

4. Flynn, A., Benn, D., Clifton-Bligh, R., Robinson, B., Trainer, A. H., James, P., … Tothill, R. W. The genomic landscape of phaeochromocytoma. Journal of Pathology. 2015. 236(1): 78–89