Single-cell and bulk gene expression analysis of rare neuroendocrine tumours | Dr Andrew Pattison

We used single nuclei RNA-Seq to better understand the relationship of tumour cells and the tumour microenvironment in phaeochromocytoma and paraganglioma.

16 September 2020

Cancer genome analyst, Rare Disease Oncogenomics Lab

University of Melbourne Centre for Cancer Research and Department of Clinical Pathology 

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that arise from the adrenal gland and the sympathetic nervous system. PPGLs are genetically diverse and  remarkable for their heritability with ~40% of cases associated with familial disease. While PPGL tumours have been previously studied using bulk tissue gene-expression methods, the analysis of individual cells in these tumours has not been previously explored.

We analysed 30 PPGL tumours and two normal adrenal tissues using a single-nuclei RNA-seq method enabling the use of frozen samples. Major and minor cell types could be identified, showing an association of cell type abundance and tumour genotype. In the tumour microenvironment, we could infer cell-cell signalling networks, involving cross talk between tumour, stroma and immune cells. Finally, we refined  PPGL subtypes integrating bulk and single-nuclei data, identifying novel PPGL subtypes and subtype specific gene-expression patterns including the expression of cell surface receptors that may be novel therapeutic and diagnostic imaging targets.

Dr Andrew Pattison completed his undergraduate degree in Biological Sciences La Trobe University, and honours year at La Trobe studying chitosan-DNA nanoparticles for DNA vaccine delivery. He moved to Monash University to. undertake a PhD studying alternative polyadenylation and RNA biology in breast cancer. There was a strong bioinformatics component to his PhD which has continued in his postdoc position at the UMCCR in the Rare Disease Oncogenomics (RADIO) lab led by Dr Richard Tothill. Currently, Dr Pattison is involved most of the lab's projects including researching rare neuroendocrine tumours and cancer of unknown primary.