Developing a multifactorial classification approach for germline variants in the colorectal cancer susceptibility genes POLE and POLD1

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Number of Honour Places Available
Clinical Pathology
Group Leader Email Number Webpage
A/Prof Daniel Buchanan 0385597004 Personal web page
Primary Supervisor Email Number Webpage
Dr Khalid Mahmood Personal web page

Project Details

In the current era of genetic testing for inherited Colorectal Cancer (CRC), multiple susceptibility genes are tested simultaneously (referred to as multi-gene panel or gene panel testing) enabling cost-effective, personalized CRC risk determination.  The increasing clinical problem resulting from multi-gene panel testing is the burden of rare genetic variants identified in these high risk genes and trying to assign pathogenicity to a variant. Recently identified CRC susceptibility genes, POLE and POLD1, have been added to these multi-gene panels without well developed and validated models for variant classification and as such, the majority of rare variants identified in POLE and POLD1 are classified as variants of uncertain clinical significance (VUS).  The classification of VUS has significant implications for patient and their family members as clinicians cannot assign the most appropriate clinical management for individual and their relatives, leaving them potentially at risk of developing CRC or being over-treated.  In this project, you will develop a multifactorial approach to variant classification for the POLE and POLD1 genes inclusive of in silico prediction tools, tumour molecular and histological features, protein structure, RNA expression, clinical and family cancer history data.  This project will develop expertise in genomics, molecular biology, bioinformatics, and statistical analysis.  The outcomes of this project will have significant international impact through improved risk categorization for patients identified to carry a rare variant in POLE and POLD1 genes.  A stipend for this project is available to the selected student.

Faculty Research Themes


School Research Themes

Cancer in Medicine

Research Opportunities

PhD, Masters by Research, Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.


Clinical Pathology

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