Assessment of the Utility of Family-based (Trio) Whole-genome Sequencing for Cancer Predisposition Testing in Sequential Newly Diagnosed Paediatric and Adolescent Cancer Patients

Brief Summary

Detailed Description

Cancer Predisposition Syndromes (CPS), caused by germline mutations in cancer predisposition genes (CPG) are heritable disorders associated with an increased risk of developing certain types of cancer. Knowledge of CPG will advance the understanding of tumorigenesis, improve patient care, and facilitate genetic counselling of patients and families. But the prevalence of CPS in Australian children with cancer and the psychosocial impact of germline sequencing to identify CPG have not been studied. The clinical benefit of family-based WGS in every new child with cancer compared with conventional predictive factors is currently unknown. By testing every child with newly diagnosed cancer the aim is to determine the utility of this approach and its impact on participants and families. The principal objective of the proposed multicentre prospective study is establish the clinical benefit and utility of family-based WGS to identify underlying CPS in every newly diagnosed child with cancer.

Primary Outcomes

Secondary Outcomes

• Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.(2 years)
• Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.(5 years)
• The proportion of patients who have de-novo vs. inherited mutation in CPG.(2 years)
• Turnaround time for issuing a report to the treating clinician.(2 years)
• The proportion of participants with a complete recording of family history of cancer.(2 years)
• Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors.(2 years)
• The proportion of individuals found to have a reportable germline mutation in a CPG(2 years)
• The proportion of participants with CPS who undergo cancer surveillance.(2 years)
• Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence.(2 years)
• Quantify the frequency of rare noncoding, complex, and oligogenic variation (in units of variants/person, and genes with variants/person), as detected by WGS, in a paediatric cancer population relative to cancer-free parents and population controls.(2 years)
• The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents.(5 years)