Identifying high-risk genes for childhood cancers

Approximately 1000 children and adolescents are diagnosed with cancer in Australia every year. However, less than 10% of all childhood tumours are associated with a known cancer predisposition syndrome. We hypothesized that whole genome analysis of DNA from affected children from families with multiple occurrences of early-onset cancers may be a valuable approach to identifying candidate genes and pathways that are associated with increased risk for childhood cancers. We performed whole genome sequencing (WGS) on 30 children enrolled in the Victorian Paediatric Cancer Family Study (VPCFS), a population-based sample of 379 children diagnosed with cancer under the age of 15 years and their families recruited from the two paediatric cancer hospitals for the state of Victoria. Further screening by targeted-sequencing of genes of interest, identified from the WGS analysis and from the literature, was performed on germline DNA from the 745 remaining VPCFS participants (including children and their relatives). This project will involve further analysis of the WGS data (including copy number variation and large rearrangement) and classification of the pathogenicity of variants identified by targeted sequencing. We anticipate that this project will reveal important insights into cancer aetiology and lead to improved cancer prevention, effective cancer screening and optimal clinical care for children with cancer and their families.