Germline Mutation, Hereditary Cancer Syndrome, High-Risk, Mutation
Conditions
Keywords
Hereditary Cancer Syndrome, High-Risk, Mutation, Germline Mutation, Rare Cancer Histology, Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES)
Brief summary
This study will investigate the utility of integrative sequencing of individuals and families at risk of hereditary cancer syndromes and will uncover novel contributors to tumourigenesis. Integrative sequencing refers to: 1. Whole genome sequencing (WGS) of the germline (inherited) genome 2. Whole exome sequencing (WES) or targeted/panel sequencing of tumour(s) (somatic, tumour-specific mutations) 3. DNA methylation (methylome) analysis of tumour(s) 4. RNA sequencing (transcriptome) of tumour(s) Eligible patients receiving genetic care at Princess Margaret Cancer Centre and the University Health Network may be approached by their genetic counsellor for participation in this study.
Interventions
None listed
Sponsors
University Health Network, Toronto
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must be ≥18 years of age 2. All patients and enrolled family members must have a signed and dated informed consent form All individuals at risk of a hereditary cancer syndrome without a known germline mutation from clinical genetic testing, will be eligible for this study. This includes: 1. Individuals with multiple primary malignancies 2. Families with a strong family history of cancer suggestive of a hereditary cancer syndrome 3. Young individuals with cancer (10 years earlier than the age of onset of sporadic cases) and no identified gene mutation 4. Rare cancer histologies Individuals with an identified germline mutation will also be eligible for this study, if there are discordant family members suggesting additional genetic factors contributing to the variable familial phenotype. For example, a family composed of mutation carriers severely affected with cancers, and carriers unaffected with cancer.
Exclusion criteria
None.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of genomic contributors to inherited cancer through genome-wide germline analysis | Through study completion, up to 3 years |
| Number of identified novel mechanisms of tumorigenesis in hereditary cancer patients | Through study completion, up to 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Utilization rate of whole genome sequencing of the germline in identifying hereditary disorders | Through study completion, up to 3 years |
| Utilization rate of genome scale/targeted analysis of tumours in identifying potential therapeutic modalities | Through study completion, up to 3 years |
Countries
Canada
Outcome results
None listed