Protocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlying cancer predisposition in paediatric and adolescent patients newly diagnosed with cancer: the PREDICT study
Yuyan Chen,
Mark Pinese,
Claire Wakefield,
Frank Alvaro,
Katherine Tucker,
Tracey A O’Brien,
Vanessa J Tyrrell,
Judy Kirk,
Kate Hetherington,
Eliza Courtney,
Kristine Barlow-Stewart,
Noemi Auxiliadora Fuentes Bolanos,
Bhavna Padhye,
Macabe Daley,
Jacqueline Hunter,
Meera Warby,
Sarah Josephi-Taylor,
Marie Wong-Erasmus,
Paulette Barahona,
Pamela Ajuyah,
Ann-Kristin Altekoester,
Loretta M S Lau,
Dianne Sylvester,
Luciano Dalla Pozza
Affiliations
Yuyan Chen
Kids Research, Children’s Cancer Research Unit, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
Mark Pinese
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Claire Wakefield
Behavioural Sciences Unit, Kids Cancer Centre, Randwick, New South Wales, Australia
Frank Alvaro
Paediatric Oncology Service, John Hunter Children’s Hospital, Hunter Region Mail Centre, New South Wales, Australia
Katherine Tucker
Nuffield Department of Primary Care Health Sciences, University of Oxford Medical Sciences Division, Oxford, UK
Tracey A O’Brien
1 Cancer Institute NSW, St Leonards, New South Wales, Australia
Vanessa J Tyrrell
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Judy Kirk
Familial Cancer Service, Westmead Hospital, Westmead, New South Wales, Australia
Kate Hetherington
School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia
Eliza Courtney
Kids Cancer Centre, Sydney Children’s Hospitals Network Randwick, Randwick, New South Wales, Australia
Kristine Barlow-Stewart
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Noemi Auxiliadora Fuentes Bolanos
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Bhavna Padhye
Cancer Centre for Children, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
Macabe Daley
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Jacqueline Hunter
Behavioural Sciences Unit, Kids Cancer Centre, Randwick, New South Wales, Australia
Meera Warby
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Sarah Josephi-Taylor
Department of Clinical Genetics, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
Marie Wong-Erasmus
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Paulette Barahona
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Pamela Ajuyah
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Ann-Kristin Altekoester
Children’s Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia
Loretta M S Lau
Kids Cancer Centre, Sydney Children’s Hospitals Network Randwick, Randwick, New South Wales, Australia
Dianne Sylvester
Kids Research, Children’s Cancer Research Unit, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
Luciano Dalla Pozza
Cancer Centre for Children, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia
Introduction Identifying an underlying germline cancer predisposition (CP) in a child with cancer has potentially significant implications for both the child and biological relatives. Cohort studies indicate that 10%–15% of paediatric cancer patients carry germline pathogenic or likely pathogenic variants in cancer predisposition genes, but many of these patients do not meet current clinical criteria for genetic testing. This suggests broad tumour agnostic germline testing may benefit paediatric cancer patients. However, the utility and psychosocial impact of this approach remain unknown. We hypothesise that an approach involving trio whole-genome germline sequencing (trio WGS) will identify children and families with an underlying CP in a timely fashion, that the trio design will streamline cancer risk counselling to at-risk relatives if CP was inherited, and that trio testing will not have a negative psychosocial impact on families.Method and analysis To test this, we present the Cancer PREDisposition In Childhood by Trio sequencing study (PREDICT). This study will assess the clinical utility of trio WGS to identify CP in unselected patients with cancer 21 years or younger in New South Wales, Australia. PREDICT will perform analysis of biological parents to determine heritability and will examine the psychosocial impact of this trio sequencing approach. PREDICT also includes a broad genomics research programme to identify new candidate genes associated with childhood cancer risk.Ethics and dissemination By evaluating the feasibility, utility and psychosocial impact of trio WGS to identify CP in paediatric cancer, PREDICT will inform how such comprehensive testing can be incorporated into a standard of care at diagnosis for all childhood cancer patients.Trial registration number NCT04903782.
