International Cancer Genome Consortium

Prostate cancer is the most common malignancy in men in the Western world; in Canada, over 25,000 men are diagnosed with prostate cancer each year, and more than 4,000 men will die of their disease.

Using the prognostic factors of T-category, serum PSA, and pathologic Gleason score (GS), men with prostate cancer are placed into low, intermediate, and high-risk groupings. These risk categories predict for biochemical recurrence, failure-free survival, and prostate cancer-specific mortality. Unfortunately, current prognostic factors can explain only a moderate proportion of variation in clinical outcome. Moreover, many low risk prostate cancers are indolent that can be safely followed in active surveillance programs, and overtreatment by radiotherapy and radical prostatectomy, particularly for PSA screen-detected cancers, causes substantial morbidity. For this reason, better predictors of treatment outcomes and patient prognosis are required to individualize prostate cancer treatment, and to provide optimal therapy with minimal side effects. It is likely that genetic prognostic and predictive tools will increase our ability to individualize treatment and provide novel therapies.

The Canadian Prostate Cancer Genome Network (CPC GENE) consists of a multidisciplinary team of biologists, oncologists, pathologists, geneticists, and specialists in bioinformatics and biostatisitics. CPC GENE will analyze single nucleotide variants, insertions, deletions, copy number changes, translocations, and other chromosomal rearrangements in 500 specimens obtained from fresh frozen tissues and blood. These patients will come from cohorts treated with radical prostatectomy and radiotherapy with at least 5 years median follow-up per cohort. In this way, CPC-GENE genomic information can be applied to novel prognostic and predictive assays in prostate cancer management.

We will derive whole genome paired-end sequences of tumour DNA with 50-fold coverage (in order to account for tumour heterogeneity and normal tissue contamination), and 30-fold coverage for germ-line DNA. In addtion, we will acquire whole-transcriptome paired-end RNA sequences of tumours (including mRNA and miRNA), and evaluate the methylation status of over 450,000 methylation sites per sample, at single nucleotide resolution.

The genetic signatures identified by CPC GENE will be used to answer questions related to inter- and intra-prostatic heterogeneity, and to identify factors that predict recurrence following surgery, radiotherapy, and hormone therapy. The results of this study should lead to important discoveries within prostate cancer biology and genetics, and will be used to select the best possible treatment for men with prostate cancer.

Robert Bristow, M.D., Ph.D., FRCPC (Project Lead)
Paul Boutros, Ph.D.
Thomas Hudson, M.D.
John McPherson, Ph.D.
Theo van der Kwast, M.D.
Lakshmi Muthuswamy Ph.D.

Project Management
Michael Fraser, Ph.D.