Integrative Sequencing in Germline and Hereditary Tumours

Active, not recruiting

• Conditions: Hereditary Cancer Syndrome; Germline Mutation; High-Risk; Mutation

• Registration Number: NCT03857594
• Lead Sponsor: University Health Network, Toronto

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-02
• Study First Submitted: 2018-10-23
• Study First Submitted QC: 2019-02-26
• Study First Posted: 2019-02-28
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-10
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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.

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Exclusion Criteria

None.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of identified novel mechanisms of tumorigenesis in hereditary cancer patients	Through study completion, up to 3 years
Number of genomic contributors to inherited cancer through genome-wide germline analysis	Through study completion, up to 3 years

Secondary Outcome Measures

Name	Time	Method
Utilization rate of genome scale/targeted analysis of tumours in identifying potential therapeutic modalities	Through study completion, up to 3 years
Utilization rate of whole genome sequencing of the germline in identifying hereditary disorders	Through study completion, up to 3 years

Trial Locations

Locations (1)

University Health Network; 🇨🇦 Toronto, Ontario, Canada