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.

cancer genetics molecular aspects molecular biology paediatric clinical genetics & dysmorphology paediatric oncology protocols & guidelines

Journal

BMJ open
ISSN: 2044-6055
Titre abrégé: BMJ Open
Pays: England
ID NLM: 101552874

Informations de publication

Date de publication:
30 05 2023
Historique:
medline: 1 6 2023
pubmed: 31 5 2023
entrez: 30 5 2023
Statut: epublish

Résumé

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. 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. 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. NCT04903782.

Identifiants

pubmed: 37253493
pii: bmjopen-2022-070082
doi: 10.1136/bmjopen-2022-070082
pmc: PMC10254808
doi:

Banques de données

ClinicalTrials.gov
['NCT04903782']

Types de publication

Clinical Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e070082

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Noemi Auxiliadora Fuentes Bolanos (NA)

Kids Cancer Centre, Sydney Children's Hospitals Network Randwick, Randwick, New South Wales, Australia.
Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.

Bhavna Padhye (B)

Cancer Centre for Children, The Children's Hospital at Westmead, Westmead, New South Wales, Australia bhavna.padhye@health.nsw.gov.au.
Kids Research, Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Macabe Daley (M)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.

Jacqueline Hunter (J)

Behavioural Sciences Unit, Kids Cancer Centre, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Kate Hetherington (K)

School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
Behavioural Sciences Unit, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia.

Meera Warby (M)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
Hereditary Cancer Centre, Prince of Wales Hospital Nelune Comprehensive Cancer Centre - NCCC, Randwick, New South Wales, Australia.

Eliza Courtney (E)

Kids Cancer Centre, Sydney Children's Hospitals Network Randwick, Randwick, New South Wales, Australia.
Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.

Judy Kirk (J)

Familial Cancer Service, Westmead Hospital, Westmead, New South Wales, Australia.
Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

Sarah Josephi-Taylor (S)

Department of Clinical Genetics, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Discipline of Genomic Medicine, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Yuyan Chen (Y)

Kids Research, Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Frank Alvaro (F)

Paediatric Oncology Service, John Hunter Children's Hospital, Hunter Region Mail Centre, New South Wales, Australia.

Kristine Barlow-Stewart (K)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
Behavioural Sciences Unit, Kids Cancer Centre, Randwick, New South Wales, Australia.

Marie Wong-Erasmus (M)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Paulette Barahona (P)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Pamela Ajuyah (P)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Ann-Kristin Altekoester (AK)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Vanessa J Tyrrell (VJ)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.

Loretta M S Lau (LMS)

Kids Cancer Centre, Sydney Children's Hospitals Network Randwick, Randwick, New South Wales, Australia.
Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.

Claire Wakefield (C)

Behavioural Sciences Unit, Kids Cancer Centre, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Dianne Sylvester (D)

Kids Research, Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Katherine Tucker (K)

Kids Cancer Centre, Sydney Children's Hospitals Network Randwick, Randwick, New South Wales, Australia.
Hereditary Cancer Centre, Prince of Wales Hospital Nelune Comprehensive Cancer Centre - NCCC, Randwick, New South Wales, Australia.

Mark Pinese (M)

Children's Cancer Institute, Lowy Cancer Centre, UNSW, Randwick, New South Wales, Australia.
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.

Luciano Dalla Pozza (L)

Cancer Centre for Children, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Tracey A O'Brien (TA)

Kids Cancer Centre, Sydney Children's Hospitals Network Randwick, Randwick, New South Wales, Australia.

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Classifications MeSH