Tumour Genomics Team

Team members

Dr Mark Cowley Dr Mark McCabe Dr Marie Wong Dr John Grady
Dr Velimir Gayevskiy Dr Nisa Sheriff Chia-Ling Chan  

Mission statement

To establish a rapid and cost-effective genomics tests for cancer diagnosis, prognosis, and risk prediction, which include whole-genome somatic cancer testing, focussed capture sequencing, and inherited cancer predisposition screening.


The comprehensive identification of genetic alterations in patient tumours offers the opportunity to substantially improve patient care, though identifying optimal therapies, obtaining a more precise diagnosis, and identifying inherited cancer risk variants. Furthermore, identifying patterns of genomic variation provides insights into the mechanisms driving cancer mutagenesis, and is revealing extensive heterogeneity over time, in response to treatment, and between patients with the same cancer diagnosis.

Led by Dr Mark Cowley, the KCCG Tumour Genomics Program develops precision cancer genomic approaches to understand individual cancer genomes, with a strong translational focus. We develop methods to analyse and interpret cancer genomic data from either targeted- or whole-genome sequencing, mostly in real time from patients enrolled onto clinical trials. We work closely with the Genomic Cancer Medicine program to deliver the genomics component of the MoST clinical trial for adults with rare and advanced cancers. Furthermore we work closely with the Children’s Cancer Institute to generate and interpret the whole genome data from the Lions Kid Cancer Genome Project. We also research the genomic basis underlying Pituitary, Lung, Head and Neck and Pancreatic Cancer.

Core research activities

Molecular Screening and Therapeutics (MoST) program

We lead the genomic analysis and interpretation component of the Molecular Screening and Therapeutics (MoST) program. Using the Illumina TruSight Tumour 170 targeted DNA and RNA sequencing panel, we are studying the actionable drivers underlying 1000 patients with rare or advanced cancers. By returning this information in real time to the MoST program, we are enrolling patients onto genotype-matched treatment arms, or providing treatment recommendations for other clinical trials.

Lions Kids Cancer Project

The Lions Kids Cancer Genome Project (LKCGP) aims to improve the outcomes for children with advanced or high-risk cancers. It is generously funded by the Lions Club International Foundation (LCIF) and the Australian Lions Childhood Cancer Foundation (ALCCRF). We are using deep whole genome sequencing to deliver individual treatment recommendations to 400 patients enrolled on the Zero Childhood Cancer (ZCC; www.zerochildhoodcancer.org.au) trial. ZCC is led by our partners at the Children’s Cancer Institute, and Kid’s Cancer Centre. Through this project, we are returning information in real time to provide personalised treatment recommendations, and in some cases, changing their diagnosis and identifying inherited cancer risk variants with important implications for other family members.

Cancer of the pituitary, head and neck

Tumours of the pituitary, head and neck represent a diverse group of malignancies that share common and significant clinical challenges. These include being frequently locally advanced when detected, cause significant morbidity and long term quality of life and due to their anatomical location are difficult to cure.

Dr Mark McCabe has developed a custom targeted sequencing gene panel to genetically characterise cancers of the pituitary and salivary glands in ~500 patients. An additional aim of this study is to characterise the genetic basis for familial pituitary tumour syndromes. Dr Vel Gayevskiy with Bruce Ashford and Ruta Gupta from SHNCI, is using targeted- and whole genome sequencing to study primary and metastatic head and neck cutaneous squamous cell carcinoma.

Tumour evolution (multi-region sequencing, liquid biopsy)

High depth temporal or spatial genomic analysis is revealing the extent to which tumours naturally evolve, throughout the course of the tumour, or in response to surgery or treatment. Approaches such as multi-region sequencing, or monitoring circulating tumour DNA from liquid biopsy are exciting opportunities for monitoring the patient journey, particularly if patients are being treated by targeted therapy.

Dr Mark Cowley, Dr Mark McCabe and Dr Vel Gayevskiy are using deep whole genome sequencing, and/or targeted sequencing to study either multiple tumours per patient, multiple timepoints, or single-timepoints. We are developing methods to understand the clonal dynamics of tumours and how they evolve over time. Collaborators include Prof Neil Watkins, Dr Ann McCormack, and Prof David Thomas.

Bioinformatic tools and resources

Flexible, cloud based genomic analysis - refynr

Analysing cancer WGS data at scale, reproducibly, and to a consistent quality is a substantial computational challenge. To meet this challenge, we developed refynr, a cloud based genomic analysis platform, utilising the DNAnexus platform. refynr is a collection of >100 software modules, and a workflow generator, which has the flexibility to analyse any type of data (targeted panel to WGS), from human disease (rare disease and cancer), for humans and mice.

Analysing cancer genomes is particularly challenging, due to issues of purity, clonality, noise, and the importance of accurately identifying somatic variants of all sizes, from single-base to whole-chromosome changes and rearrangements. We are constantly optimising our somatic analysis platform to improve the accuracy of the variant calls, expanding the breadth of annotation, and the breadth of analysis into signatures, drivers and therapeutic targets.


Making sense of the millions of genetic variants present in a genome is extremely challenging. To address this challenge, Dr Vel Gayevskiy has led the development of Seave (www.seave.bio), a researcher- and clinician-friendly, web-based platform for filtering variants. It allows variants from WGS, exomes or targeted sequencing to be annotated, and filtered according to inheritance models, pathogenicity, rarity, and implication in known disease. By making it straightforward to curate gene lists, users can restrict their search to genetic variants to only those genes associated with the patient phenotype. Importantly, it stores short variants alongside CNV and SV, allowing integrated variant queries to be performed. Seave is being widely used for diagnosing patients with Mendelian disorders, rare disease gene discovery, genomics education, inherited cancer risk assessment, and somatic cancer genomics.

Dr Velimir Gayevskiy is the main developer of Seave, who is working closely with Dr Mark Cowley and clinical geneticists, medical specialists and genetic pathologists within Genome.One to continue to develop Seave to solve the needs of both rare disease, and cancer research. Access to Seave is on a collaborative basis.

Automated variant interpretation, diagnosis and reporting

Through our translational research, we need to return clinically relevant tumour mutations for dozens of patients per week. We have written tools to automate the filtering and identification of variants (auto-Seave; Marie Wong), integrate the disparate types of genomic variants together (glooee; Marie Wong) or CNV with SV from targeted sequencing (John Grady), and near-automatically generate molecular tumour board reports (John Grady). These innovations are important infrastructure for delivering precision cancer genomics on campus. Ongoing efforst in this space include variant curation and sharing platforms, and improved knowledge bases of important variants, drugs, trials and their actionability.


Garvan collaborations

Cancer Genomic Medicine Program
Prof David Thomas, Dr Mark Pinese

Lung & Head & Neck Cancer laboratory
Prof Neil Watkins

Tumour Progression laboratory
A/Prof Alex Swarbrick

Personalised Cancer Therapeutics laboratory
Dr Marina Pajic

Tumour Development laboratory
Dr David Gallego-Ortega

Colon and Lung Cancer laboratory
A/Prof Maija Kohonen-Corish

External collaborations 

Sydney Head and Neck Cancer Institute
Dr Bruce Ashford, A/Prof Ruta Gupta, Prof Jonathan Clark

University of Wollongong
Dr Marie Ranson

Children’s Cancer Institute
Prof Michelle Haber, Vanessa Tyrrell, Dr Emily Mould, Dr Chelsea Mayoh, Paulette Barahona

Sydney Children’s Hospital
Prof Glenn Marshall
David Ziegler

Murdoch Children’s Research Institute
A/Prof Paul Eckert

Peter MacCallum Cancer Centre
Dr Amit Kumar, Prof Tony Papenfuss, Dr Andrew Fellowes, Dr Ken Doig

Hartwig Medical Foundation
Peter Priestley

Asbestos Diseases Research Institute
Glen Reid

Monash University
Arun Azad