Integrative Sequencing In Germline and Hereditary Tumours

Study Overview
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Brief Summary
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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: Whole genome sequencing (WGS) of the germline (inherited) genome Whole exome sequencing (WES) or targeted/panel sequencing of tumour(s) (somatic, tumour-specific mutations) DNA methylation (methylome) analysis of tumour(s) 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.

Official Title
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Integrative Sequencing In Germline and Hereditary Tumours

Conditions
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Hereditary Cancer Syndrome, High-Risk, Mutation, Germline Mutation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥18 years of age 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: Individuals with multiple primary malignancies Families with a strong family history of cancer suggestive of a hereditary cancer syndrome Young individuals with cancer (10 years earlier than the age of onset of sporadic cases) and no identified gene mutation 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals at risk of hereditary cancer syndrome<br>All individuals at risk of a hereditary cancer syndrome with or without a known germline mutation from clinical genetic testing. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rare Cancer Histology, Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), Hereditary Cancer Syndrome, High-Risk, Mutation, Germline Mutation