Research identifies markers of metastases for rare adrenal cancer patients

New research has used single cell genomic technologies to dissect the cellular makeup and transcriptional programs of rare neuroendocrine tumours, providing important information for the development of new diagnostics and therapeutics.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that arise from cells of the autonomic nervous system. These tumours are highly hereditary and can overproduce hormones such as adrenaline that causes high morbidity and potentially life-threatening conditions in patients. In 10 to 20 per cent of cases, these tumours will also metastasise and become incurable. There is a clinical need to identify reliable biomarkers of metastatic progression as well as improved treatments.

The research, published in Nature Communications, was led by Associate Professor Richard Tothill at the University of Melbourne Centre for Cancer Research and Department of Clinical Pathology, with collaborators from National Institute of Health (USA); Peter MacCallum Cancer Centre; Palacky University Olomouc (Czech Republic); University of Colorado, Tufts Medical Centre, University of Texas (United States); Kolling Institute and Royal North Shore Hospital, Sydney.

The group used single nuclei RNA-seq and bulk tissue gene expression data to study in exquisite detail the cellular composition of these neuroendocrine tumours comparing their results to normal adrenal tissues helping to identify distinct tumour and normal cell gene expression programs associated with clinical behaviours.

Associate Professor Tothill said that a better understanding of the molecular and cellular characteristics of the disease was vital to improve future treatments.

"Our work confirms a strong link between mutated driver genes and transcriptional programs of tumour cells, in particularly, a cellular program driving a highly vascular tumour microenvironment with some novel disease subtype associations made in this regard”.

"A better understanding of the molecular landscape of these tumours and the identification of new diagnostic and therapeutic biomarkers provides important and exciting leads for further investigation, which may lead to novel functional imaging tracers and treatments in the future."