Cohort: Cancer

This sequencing project will help improve cancer care for Canadians with hereditary cancer risk through enhanced, genomics-based screening.

Abstract: Less than 10 per cent of Canadians with hereditary cancer risk have been identified, due to under referral of eligible patients, limited capacity of cancer genetic services and low rates of cascade genetic testing. Several measures have been put in place in British Columbia and the Yukon to improve efficiencies and scale services. Universal multigene panel testing has standardized molecular genetic assessment across the main indications for service delivery since 2014 and has built experience with variants of uncertain significance and secondary findings. Introduction of Oncologist-initiated testing, and now “Mainstreamed testing” with providers returning the result, has enabled consent for genetic testing by non-genetics providers outside of BC Cancer's Hereditary Cancer Program (HCP) and has shown improved access, enhanced uptake, faster results and more equitable care. Oversight has been achieved through a lab-embedded genetic counselling team that reviews all mainstreamed testing and reflexively refer cases to HCP with positive results (10 per cent), concerning personal or family cancer history, or those with concerning variants of uncertain significance. To address a waitlist and capacity issues within HCP, a digital portal was introduced and is offered to all HCP patients to standardize pretest information, enable consent and faster access to testing. Routine patient reported outcome measures have enabled monitoring and cross-comparison of new modes of service delivery to ensure non-inferiority. These collective measures have positioned HCP's next move to whole genome sequencing, where the Cancer Genetics and Genomics Lab is currently introducing a virtual hereditary cancer gene panel on a clinical genome backbone, to be routinely offered to HCP and mainstreamed patients. To facilitate health system learning, variant interpretation, clinical advancement and ongoing research, patients can join the Canadian Precision Health Initiative (CPHI) by consenting to share deidentified health and genomic data. Once a hereditary cancer patient is molecularly diagnosed, identifying the parental origin of a variant is a key limitation of genetic testing. CPHI-consenting patients with positive results will be offered our novel Parent-of-Origin-Aware genomic analysis (POAga) method, that accurately predicts which parental line a variant is from. The HCP uses the POAga research prediction to direct clinical cascade genetic testing to families supports targeted cascade testing within families.

Deliverables:

1. 6,585 Short-Read Genomes from a diverse patient cohort.
2. 900 Long-Read Phased Genomes with parent-of-origin data (POAga).
3. 40 Diverse POAga Carriers to promote cascade genetic testing.
4. 60 POAga-characterized Parent-Child Trios. These deliverables advance genetic assessment, improve cascade testing and ensure diverse representation, positioning Canada as a leader in hereditary cancer care and parent-of-origin-aware genomic analysis.

As well as receiving funding from Innovation, Science and Economic Development Canada (ISED) through Genome Canada, this project is supported by Government of Canada funding from the Canadian Institutes of Health Research (CIHR) Institute of Cancer Research (ICR).