International Cancer Genome Consortium

One in 75 men and women will be diagnosed with pancreatic ductal adenocarcinoma during their lifetime. Most will succumb to their disease within one year following diagnosis with an overall 5-year relative survival rate of only 5% - an outcome that has not appreciably changed since the 1970s. The vast majority (80% or greater) of pancreas cancer cases are diagnosed after the cancer has spread to regional lymph nodes or more distal metastases. Unlike many other cancers, PDAC has remained recalcitrant to advanced treatments with little benefit seen from new therapeutics and targeted strategies. Identifying the molecular mechanistic undercurrent behind the disease will provide opportunities for developing strategies for prevention, treatment and early detection of PDAC.

As a contributing member of the ICGC, the OICR will generate a comprehensive catalogue of genomic abnormalities found in pancreatic tumours. Our target is to collect the requisite 500 independent tumours and their matched controls and fully characterize 350 of these. The reduced number analyzed reflects a collaboration with the Australian teams in Sydney and Brisbane that are leading a parallel ICGC project targeting pancreatic cancer and who will analyze similar numbers (Drs. Sean Grimmond and Andrew Biankin). In order to ensure compliance with ICGC informed consent for large-scale sequencing, most samples will be collected prospectively with a few existing samples used for testing purposes only. In addition, we will establish xenografts from all samples in order to generate models for target validation and preclinical studies. Analyses will include whole genome sequencing of selected samples and for all samples: exome, whole transcriptome and miRNA sequencing; as well as structural and copy number variation determination. Complementary studies will include copy number determination using microarray technologies, DNA methylation analysis and functional studies using cell lines and xenografts.

Sample acquisition will require the collaboration of multiple sites. The OICR has established collaborations locally, at the Mayo Clinic, Rochester, and with Harvard Medical School and Massachusetts General Hospital, Boston to meet this demand. Locally, Drs. Steven Gallinger, Ming-Sound Tsao and David Hedley, provide substantial expertise in pancreatic cancer pathology and etiology. Drs. Gloria Petersen and Debrabata Mukhopadhyay will lead the Mayo Clinic collaboration. Drs. Sarah Thayer, Lynda Chin and Ron DePinho are coordinating collaborative efforts at the Boston-area Hospitals.

• John D. McPherson, Ph.D.
• Thomas Hudson, M.D.
• Lincoln Stein, M.D., Ph.D.