Our group aims to identify causative germline alterations in cancer predisposition genes in children with cancer.

Germline alterations in cancer predisposition genes (CPGs) are associated with increased risk of developing certain cancers. Identifying the underlying germline genetic contribution to cancer development in children can assist in developing personalised treatment, early detection, and provide risk clarification and guidance for the family. Currently it has been reported that 10-15% of paediatric patients with cancer carry germline pathogenic variants in known CPGs. 

Our team has developed research expertise in the detection and analysis of cancer predisposition in the germline of children with cancer during the last decade. Data from our team provided the pilot evidence for subsequent launch of the PREDICT trial across NSW (cancer PREDIsposition in Childhood by Trio-based sequencing). We have also established a Paediatric Cancer Genetics Service (Clinic) at The Children’s Hospital at Westmead in 2023 to care for children and families with underlying cancer predispositions.

Currently there is a proportion of patients who have features suggestive of underlying cancer predisposition but no pathogenic alterations identified in known CPGs. To further expand our knowledge on cancer predisposition, our team are developing bioinformatics pipelines to comprehensively analyse the whole exome/genome sequence data from our study cohort to identify novel candidate cancer predisposition genes/variants. With our expertise in curation of pathogenic germline variants and functional biology, we aim to identify novel variants and analyse prioritised variants/genes through functional analysis platforms using advanced methodologies such as CRISPR-Cas9 genome editing and induced pluripotent stem cell models. Our work will advance current understanding of childhood cancer predisposition and facilitate personalised medical care for patients harbouring such germline alterations, which will ultimately lead to cancer prevention and better quality of life.