Personalized Oncogenomics (POG) Program of British Columbia

Carcinogenesis is an immensely complex process such that even within a histologic cancer subtype - for example adenocarcinoma of the lung or breast - there is significant variability in cancer behaviour and response to therapy. Analyses of individual patients demonstrate unique molecular signatures for every cancer examined. Frequently, multiple different pathways are involved in disease growth and progression and the dominant process varies from person to person and perhaps even within different sites of disease within one person. As well these variations evolve in response to treatment.

Recognizing genetic aberrations that promote disease facilitates targeted treatment; this has been demonstrated in several small subgroups of cancers in which specific genetic mutations or translocations have been successfully treated with targeted chemotherapy agents. With many recognized mutations and aberrations, personalized evaluation of the genetic signature encoded in DNA and RNA may provide important diagnostic information and potentially enable directed therapy to the appropriate oncologic pathway thereby providing information to help guide chemotherapy choices

Our initial pilot project demonstrated the feasibility of this approach at our institution (with 100 patients). We now know it is possible to identify and consent patients, sequence the genome and transcriptome, analyze and report abnormalities, and identify potential actionable targets in a clinically relevant time frame.

The Personalized OncoGenomics (POG) program has been operational across the province of BC since 2012. The initial two-year phase established the infrastructure and workflow by which patients with metastatic or incurable cancers could be identified, consented, and biopsied for genomic sequencing in a clinically accredited lab (Laskin et al., 2015). The next phase of the POG program (2014 - 2017) included a strong educational and engagement process such that 83 (80%) of the medical oncologists at BC Cancer were trained to consent and enroll patients onto POG. This means that the oncology community in BC has a broad education in cancer genomics and how these data may be applied to individual patients. Since 2017, the program has been integrated into the Vancouver Cancer Centre's phase 1 clinical trials unit and the focus has shifted to use the study patients and data to address more focused clinical therapeutic trials such as the CCTG CAPTUR study (Skamene et al., 2018). POG-like WGTA has been the driving force behind the creation of the Terry Fox Marathon of Hope Cancer Centre Network (MOHCCN) which is a national program for cancer genomic data sharing across Canada.

The overarching theme of this POG Program is to create a comprehensive cataloguing of somatic cancer mutations and cellular pathway abnormalities that could generate profound insights into genetic patterns that underlie particular cancer phenotypes, and provide valuable prognostic and predictive information.

Eligible subjects will have several samples analyzed: a fresh tumour biopsy (typically 5 cores are required), a blood sample for normal comparison and archival tumours when available. Also, technology has improved such that we may consider using paraffin embedded materials. Comprehensive DNA and RNA sequencing is performed followed by an in-depth bioinformatic analysis to identify somatic mutations, gene expression changes or other abnormalities that might be cancer "drivers" or provide actionable (diagnostic) or druggable targets. The POG team meets every week to discuss the detailed genomic reports for patients, consider additional validation tests when necessary, and debate research questions. The clinicians (typically 5 - 10) come to a consensus on what systemic therapies might be appropriate based on these results. Whenever possible subjects are matched to clinical trials.