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Early Experiences From BC Cancer Agency's Personalized Oncogenomics Project Shared at ASHG

VANCOUVER, British Columbia (GenomeWeb) – At the American Society of Human Genetics annual meeting here yesterday, the BC Cancer Agency's Marco Marra shared his team's experiences with the first few hundred adult and pediatric cancer cases assessed through the ongoing Personalized Oncogenomics (POG) clinical trial.

Speaking as part of an Illumina-sponsored workshop at the conference, Marra noted that roughly 700 individuals have been enrolled in POG since the main project began in 2015, with more than 400 adult cases and nearly three-dozen pediatric cases sequenced so far.

Back in 2010, Marra and his colleagues reported in Genome Biology that they were able to uncover clinically informative driver alterations in an adenocarcinoma of the tongue that was sequenced at diagnosis and again after targeted kinase inhibitor treatment. That led to a 2012 pilot study of individuals with advanced, incurable cancer. And with the help of new funding from the BC Cancer Foundation, POG kicked off in 2015 with the goal of sequencing 300 cancer genomes.

The project has grown since then and is now set to include at least 2,000 or more children or adults with cancer in British Columbia — a Canadian province of 4.5 million people with a faster-aging population than many other parts of the country.

Earlier this year, BC premier Christy Clark announced that the BC Cancer Agency will receive C$3 million (US$2.1 million) to support personalized cancer treatment strategies such as POG through the BC Cancer Foundation.

Marra outlined the pipeline for the POG trial, from the informed consent step to matched tumor-normal sample sequencing — 80-fold average tumor genome or biopsy coverage and 40-fold coverage of normal samples, on average — to rapid analyses focused on finding informative changes, followed by more in-depth dives into the sequence data to search for less obvious clinical suspects.

Oncologists, genetics researchers, and other experts involved in POG typically meet weekly to discuss potential treatment options, Marra said, turning over the manually curated alterations identified in the whole-genome and transcriptome sequences.

He highlighted the importance of carefully considering the available data types when making cancer treatment decisions, particularly gene expression patterns gleaned from RNA-seq data produced for POG.

Nevertheless, Marra noted that not all of the actionable changes detected in individuals' genome and transcriptome sequences are yet being used to guide treatment. In some cases patients may already be responding well to the treatment they are on, for example, while other cases may involve targets for drugs that are not accessible.

Indeed, drug access is one of the challenges that remain when applying genome and transcriptome sequencing to cancer cases, according to Marra and his colleagues.

"Most actionable findings from POG are targeted chemotherapy agents either approved or in clinical trials," they wrote in a 2015 paper for the Cold Spring Harbor journal Molecular Case Studies that discussed findings for 100 adult cancer cases assessed for the POG pilot study. "For genomics to be truly integrated as a decision-making tool these treatments need to be available and thus an active clinical trials program is critical."

And there are other hurdles to overcome as personalized oncogenomics moves toward the clinic, Marra explained. For example, he said the approach is still relatively time-consuming and expensive, coming in at a price tag of $19,000 per case, on average, in the POG trial. The existing strategy also does not take into account the heterogeneity of tumor samples and the dynamics of an individual's cancer over time.