Assessment of the utility of family-based (trio) whole-genome sequencing for cancer predisposition testing in sequential newly diagnosed paediatric and adolescent cancer patients
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.
Study Type
OBSERVATIONAL
Enrollment
270
1. Germline whole-genome family-based sequencing and variant identification. 2. Multidisciplinary Meeting case discussion. 3. Recommendation of referral to a Cancer Genetics Clinic for further investigation, follow up and/or genetic counselling. 4. Psychosocial study to analyse the impact of germline sequencing on families.
John Hunter Children's Hospital
Newcastle, New South Wales, Australia
RECRUITINGSydney Children's Hospital
Sydney, New South Wales, Australia
RECRUITINGThe Children's Hospital at Westmead
Sydney, New South Wales, Australia
RECRUITINGThe proportion of patients with CPS identify by WGS as compared to those correctly identified by clinical information (i.e. family history, tumour type, physical findings).
Time frame: 2 years
The proportion of individuals found to have a reportable germline mutation in a CPG
Time frame: 2 years
The proportion of patients who have de-novo vs. inherited mutation in CPG.
Time frame: 2 years
Turnaround time for issuing a report to the treating clinician.
Time frame: 2 years
The proportion of participants with a complete recording of family history of cancer.
Time frame: 2 years
Sensitivity and specificity of WGS versus single/multiple gene panel testing guided by clinical predictive factors.
Time frame: 2 years
The proportion of participants with CPS who undergo cancer surveillance.
Time frame: 2 years
Test the significance of common cancer risk polymorphisms within a family as a contributing factor in cancer incidence.
Time frame: 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.
Time frame: 2 years
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Assess the prevalence of subclonal somatic variation (e.g. clonal haematopoiesis of indeterminate potential) in children with non-haematological cancer.
Time frame: 2 years
The psychological impact of the germline sequencing process, including the informed consent process, on patients and parents.
This will be achieved through identifying the incidence of patients and parents enrolled in the study experiencing clinically significant levels of distress, defined as a \>7 rating on any of the outcome measures in the Emotion Thermometers Tool©. The incidence of parents and patients experiencing other psychological outcomes such as reduced quality of life will also be identified using the validated scales EuroQoL EQ-5D-5L (parent proxy)/EQ-5D-Y (youth version), Decisional Regret Scale and the Trust In Physician Scale (adapted for a paediatric setting). Psychological outcomes will be re-assessed over the 5 year course of the study to assess impacts of germline sequencing over time.
Time frame: 5 years
Cost of clinical model including WGS for cancer predisposition testing in every child newly diagnosed with cancer.
Time frame: 5 years