Clinical trial NCT03857594: Integrative Sequencing in Germline and Hereditary Tumours
Official title: Integrative Sequencing in Germline and Hereditary Tumours
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Hereditary Cancer Syndrome
High-Risk
Mutation
Germline Mutation
Keywords: Hereditary Cancer Syndrome
High-Risk
Mutation
Germline Mutation
Rare Cancer Histology
Whole Genome Sequencing (WGS)
Whole Exome Sequencing (WES)
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-02-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All individuals at risk of a hereditary cancer syndrome with or without a known germline mutation. This includes individuals with multiple primary malignancies, families with a strong family history of cancer, young individuals with cancer, rare cancer histologies.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of genomic contributors to inherited cancer through genome-wide germline analysis
timeFrame: Through study completion, up to 3 years
measure: Number of identified novel mechanisms of tumorigenesis in hereditary cancer patients
timeFrame: Through study completion, up to 3 years
Secondary outcomes:
measure: Utilization rate of whole genome sequencing of the germline in identifying hereditary disorders
timeFrame: Through study completion, up to 3 years
measure: Utilization rate of genome scale/targeted analysis of tumours in identifying potential therapeutic modalities
timeFrame: Through study completion, up to 3 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Raymond Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: