Integrative Sequencing In Germline and Hereditary Tumours

NCT03857594 | Active Not Recruiting

• 1 other identifier: INSIGHT
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

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. 1.Whole genome sequencing (WGS) of the germline (inherited) genome
2. 2.Whole exome sequencing (WES) or targeted/panel sequencing of tumour(s) (somatic, tumour-specific mutations)
3. 3.DNA methylation (methylome) analysis of tumour(s)
4. 4.RNA sequencing (transcriptome) of tumour(s)

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)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (1)

Individuals at risk of hereditary cancer syndrome

All individuals at risk of a hereditary cancer syndrome with or without a known germline mutation from clinical genetic testing.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• None.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, Canada

Location

Related Publications (1)

• Wang Y, Ding Q, Prokopec S, Farncombe KM, Bruce J, Casalino S, McCuaig J, Szybowska M, van Engelen K, Lerner-Ellis J, Pugh TJ, Kim RH. Germline whole genome sequencing in adults with multiple primary tumors. Fam Cancer. 2023 Oct;22(4):513-520. doi: 10.1007/s10689-023-00343-2. Epub 2023 Jul 22.

  PMID: 37481477 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Archival tumor tissue, whole blood at baseline for germ-line DNA analysis

MeSH Terms

Conditions

Neoplastic Syndromes, Hereditary

Condition Hierarchy (Ancestors)

Neoplasms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Raymond Kim, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: February 28, 2019
• Study Start: October 2, 2018
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

CA (1)