Predict Cancer Predisposition Screening

We launched the PREDICT trial, a first in class complex, cross-disciplinary, multi-institutional, prospective clinical trial, whose primary aim is to understand the inherited risk of cancer in children and determine the psychosocial impact of family- based germline whole-genome sequencing in children and families. Using these insights to support and educate health professionals in the evolving area of precision medicine.

This work has helped us understand the full spectrum of cancer genetic risk variants and how prevalent they are in children with cancer, and when a child has a particular variant, how likely it is to contribute to the risk of cancer developing in that child. This is important information to inform management of cancer, and for families to make choices about future pregnancies and minimise their own risk.

Lead Investigators

• Dr Luciano Dalla Pozza, Director Cancer Centre for Children, Children’s Hospital at Westmead
• A/Professor Kathy Tucker, Cancer Clinical Geneticist, Prince of Wales Hospital and Kids Cancer Centre, Sydney Children’s Hospital at Randwick
• A/Professor Vanessa Tyrrell Program Leader, Zero Childhood Cancer Co-Head of Theme, Personalised Medicine, Children’s Cancer Institute
• A/Professor Mark Cowley, Head, Computational Biology Group, Children’s Cancer Institute
• Professor Claire Wakefield, [Past] Head, Behavioural Sciences Unit, Kids Cancer Centre, Sydney Children’s Hospital, Randwick School of Women’s and Children’s Health, UNSW Sydney
• A/Professor Judy Kirk, Director, Familial Cancer Service Westmead Hospital
• A/Professor Tracey O’Brien, [Past] Director, Kids Cancer Centre, Sydney Children’s Hospital at Randwick
• Professor Jennifer A. Byrne, Director of Biobanking, NSW Health Pathology and Professor of Molecular Oncology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney

Research Team

• A/Professor Kristine Barlow-Stewart, Senior Genetic Counsellor, Zero Childhood Cancer, Snr Research Genetic Counsellor, Centre for Clinical Genetics Sydney Children’s Hospital at Randwick
• Dr Yuyan Chen, Children’s Cancer Research Unit, University of Sydney
• Dr Noemi Fuentes-Bolanos Research Fellow, Kids Cancer Centre, Sydney Children’s Hospital at Randwick
• Dr Kate Hetherington, Behavioural Sciences Unit, Kids Cancer Centre, Sydney Children’s Hospital, Randwick, School of Women’s and Children’s Health, UNSW Sydney
• Dr Joice Kuroiwa-Trzmielina Research Administration Coordinator Children’s Cancer Institute
• A/Professor Geraldine O’Neill Children’s Cancer Research Unit University of Sydney
• Dr Mark Pinese, Senior Bioinformatics Research Officer, Children’s Cancer Institute
• Dr Bhanva Padhye Research Fellow, Cancer Centre for Children, Children’s Hospital at Westmead
• Dr Dianne Sylvester, Children’s Cancer Research Unit, University of Sydney

• Children’s Cancer Institute (Australia)
• Children’s Medical Research Institute (Australia)
• UNSW Sydney (Australia)
• University of Sydney (Australia)
• Kids Cancer Centre Sydney Children’s Hospital, Randwick, Sydney Children’s Hospitals Network (Australia)
• Children’s Cancer Research Unit, Cancer Centre for Children, Department of Genetics, Children’s Hospital Westmead, Sydney Children’s Hospitals Network (Australia)
• Zero Childhood Cancer national and international partners network (8 hospitals, >20 research institutes), incl. all three NSW Paediatric Oncology Centres, Children’s Hospital Westmead, Sydney Children’s Hospitals Network, John Hunter Children’s Hospital, and Sydney Children’s Hospital, Randwick (Australia)
• Hereditary Cancer Centre, Prince of Wales Hospital, Randwick (Australia)
• Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital (Australia)
• Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research (Australia)
• Behavioural Sciences Unit, Kids Cancer Centre, Randwick, UNSW School for Women’s and Children’s Health (Australia)
• Consumer representative groups

Thomas – predict patient story

Thomas – predict patient story

Are some children predisposed to cancer? 

Predisposition screening for cancers

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

NSW-Advanced-Therapeutics-Ecosystem-Prosp 11 ZEROCancer

Bolanos NA, Padhye B, Daley M, Hunter J, Hetherington K, Warby M, Courtney E, Kirk J, Josephi-Taylor S, Chen Y, Alvaro F. Protocol: 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. BMJ Open. 2023;13(5).

Wong M, Mayoh C, Lau LM, Khuong-Quang DA, Pinese M, Kumar A, Barahona P, Wilkie EE, Sullivan P, Bowen-James R, Syed M. Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer. Nature medicine. 2020 Nov;26(11):1742-53.

Sylvester DE, Chen Y, Grima N, Saletta F, Padhye B, Bennetts B, Wright D, Krivanek M, Graf N, Zhou L, Catchpoole D. Rare germline variants in childhood cancer patients suspected of genetic predisposition to cancer. Genes, Chromosomes and Cancer. 2022 Feb;61(2):81-93.

Goudie C, Witkowski L, Cullinan N, Reichman L, Schiller I, Tachdjian M, Armstrong L, Blood KA, Brossard J, Brunga L, Cacciotti C. Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for identifying cancer predisposition syndromes. JAMA oncology. 2021 Dec 1;7(12):1806-14.

Lau LMS, Mayoh C, Xie J, Barahona P, MacKenzie KL, Wong M, Kamili A, Tsoli M, Failes TW, Kumar A, Mould EVA, Gifford A, Chow SO, Pinese M, Fletcher JI, Arndt GM, Khuong-Quang DA, Wadham C, Batey D, Eden G, Trebilcock P, Joshi S, Alfred S, Gopalakrishnan A, Khan A, Grebert Wade D, Strong PA, Manouvrier E, Morgan LT, Span M, Lim JY, Cadiz R, Ung C, Thomas DM, Tucker KM, Warby M, McCowage GB, Dalla-Pozza L, Byrne JA, Saletta F, Fellowes A, Fox SB, Norris MD, Tyrrell V, Trahair TN, Lock RB, Cowley MJ, Ekert PG, Haber M, Ziegler DS, Marshall GM. In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer. EMBO Mol Med. 2022 Apr 7;14(4):e14608. doi: 10.15252/emmm.202114608. Epub 2021 Dec 20.

Hetherington, K., Hunter, J.D., Lockridge, L, Warby, M., Raygadam, M., Wakefield, C.E. & Wiener, L. The psychosocial impacts of familial endocrine cancer syndromes (FECS) on the patient and caregiver. [Chapter in book] Familial Endocrine Cancer Syndromes: Navigating the Transition of Care for Pediatric and Adolescent Patients. Fady Hannah-Shmouni (Editor), Springer. [In Press].

Fuentes-Bolanos, N., Padhye, B., Daley, M., Hunter, J.D., Hetherington, K., Warby, M., Courtney, E., Kirk, J., Josephi-Taylor, S., Chen, Y., Alvaro, F., Barlow-Stewart, K., Wong-Erasmus, M., Barahona, P., Ajuyah, P., Altekoester, AK., Lau, L., Wakefield, CE., Sylvester, D., Tucker, K., Pinese, M., O’Brien, TA., Dalla Poza, L. 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. BMJ Open 2023;13:e070082. doi: 10.1136/bmjopen-2022-070082.

McGill, B. C., Wakefield, C. E., Tucker, K. M., Daly, R. A., Donoghoe, M. W., Vetsch, J., Warby, M., Fuentes-Bolanos, N. A., Barlow-Stewart, K., Kirk, J., Courtney, E., O’Brien, T. A., Marshall, G. M., Pinese, M., Cowley, M. J., Tyrrell, V., Deyell, R. J., Ziegler, D. S., & Hetherington, K. Parents’ expectations, preferences, and recall of germline findings in a childhood cancer precision medicine trial. Cancer. 2023; 1- 13.