Cancer Genetics Adrenal Laboratory
Head of laboratory
On this page:
- Overview of research program
- Major funding sources
- Selected publications
- Major collaborations
- Research project opportunities
The Cancer Genetics Adrenal Laboratory studies neoplasms of the adrenal cortex (adrenocortical tumours) and of the adrenal medulla (phaeochromocytomas). Overall the work focuses on discovering markers to assist with the early identification of malignancy, and finding genes which will lead to a greater understanding of the pathogenesis of adrenal tumours and thereby ultimately improving the clinical management of these patients and their families.
Our microarray profiling studies of adrenocortical tumours have revealed a number of genes to have altered expression when comparing benign to malignant tumours. At this hospital, immunohistochemical staining of two of these markers, IGF-II and Ki-67 has now been incorporated into pathology assessment of adrenocortical tumours to assist with accurate diagnosis and predicting the course of disease. Currently we are investigating other diagnostic targets to distinguish adrenocortical carcinomas from adenomas and therapeutic targets in the treatment of adrenocortical carcinomas.
Further work focuses on the function of key differentially expressed genes and using cell culture systems to study the mechanism of action of adrenolytic agents, with the aim of discovering molecular markers involved in diagnosis, prognosis and response to therapy.
Phaeochromocytomas are rare tumours of the adrenal medulla, frequently causing an increase in the production of adrenalin and resulting in a life threatening elevation in blood pressure. Approximately 30% of phaeochromocytomas are hereditary and germline mutations of RET, VHL and genes encoding 3 subunits of succinate dehydrogenase (SDH), SDHB, SDHC, SDHD have been identified as the cause. However there is no reliable marker to differentiate benign from malignant disease and current gene profiling studies are investigating potential markers to predict the course of disease.
Additional studies are investigating the functional consequences induced by different SDHB truncating and missense mutations on complex II mitochondrial activity using phaeochromocytoma cell models. In vitro studies have shown differing effects on growth between wild type and mutant SDHB sequences and the cellular signalling molecules that may be contributing to this are under investigation.
- National Health & Medical Research Council
- Cancer Institute NSW
- Hillcrest Foundation
- Mary Debattista Fund
- Royal Australasian College of Surgeons
Soon PS, Libe R, Benn DE, Gill A, Shaw J, Sywak MS, Groussin L, Bertagna X, Gicquel C, Bertherat J, McDonald KL, Sidhu SB, Robinson BG. Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors. Ann Surg. 2008 Jan;247(1):157-64
Adler JT, Meyer-Rochow GY, Chen H, Benn DE, Robinson BG, Sippel RS, Sidhu SB. Pheochromocytoma: current approaches and future directions. Oncologist. 2008 Jul;13(7):779-93. Epub 2008 Jul 10.
Benn DE, Richardson AL, Marsh DJ, Robinson BG. Genetic testing in pheochromocytoma- and paraganglioma-associated syndromes. Ann N Y Acad Sci. 2006 Aug;1073:104-11. Review
Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes.J Clin Endocrinol Metab. 2006 Mar;91(3):827-36. Epub 2005 Nov 29.
- Dr Anthony Gill (Department of Anatomical Pathology, PaLMS, RNSH)
- Dr Leigh Delbridge (Department of Endocrine & Oncological Surgery, RNSH)
- Dr Mark Sywak (Department of Surgery, RNSH)
- Dr Michael Yeh (UCLA, USA)
- Dr Anthony Gill (Department of Anatomical Pathology, RNSH)
- Professor Hartmut Neumann (Freiburg, Germany)
- Dr Mike Croxson (Auckland New Zealand), Dr Kathy Tucker (Prince of Wales Hospital and University of NSW)
- Dr Leigh Delbridge (Department of Endocrine and Oncological Surgery RNSH)
- Dr Mark Sywak (Department of Surgery RNSH)