Beating Cancer With Better Research Tools: How Ontario Is Working With The World To Crack The Genomics Of Cancer

---

By Shawn Lawrence

On April 29, cancer institutes around the world banded together to launch the International Cancer Genome Consortium (ICGC), a massive global initiative that will see researchers attempt to crack the genomics of 50 of the most common cancers plaguing mankind.

The potential for this project is substantial, and according to many in the know it represents the largest global research collaboration since scientists worked together to crack the human genome.

The benefits would mean a better understanding of the genomic roots of cancer and would lead to new ways to detect, treat and ultimately prevent many forms of this devastating disease.

Ontario is set to be a major player in this exciting yet massive effort. With its extensive research capacity, a complement of top-level scientists and a strong tradition of biomedical discovery, scientists at the Ontario Institute for Cancer Research (OICR) will study the genomic changes involved in pancreatic cancer, while also hosting the secretariat to coordinate the work on other cancer types to be undertaken by research centres from eight other countries, including Australia, Britain, China, France, India, Japan, Singapore and the United States. Backed by the provincial government’s contribution of $40 million, the Institute has purchased cutting edge DNA sequencing machines, lured in top talent, will carry out cancer genomics research and will serve as the global centre to the largest health informatics database in history. It will also oversee its operations in the role of secretariat.

Launched by the provincial government in 2005, the OICR is no stranger to science on a large scale. In the past, the institute was the first organization to pledge funds to support the collaboration efforts between researchers and scientists in Ontario and California and in the creation of the Cancer Stem Cell Consortium (see “Across Canada Q&A,” August 2007 Biotechnology Focus, page 22). Similarly, OICR was heavily involved along with the US National Institutes of Health and UK Wellcome Trust during the initial planning stages for ICGC. For many reasons OICR was considered a viable candidate to host both the ICGC’s secretariat and data coordination centre.

Tom Hudson, who is the OICR’s president and scientific director and a member of the Consortium’s interim executive committee, explains that building collaborations such as the ICGC is exactly what OICR was created to do, while at the same time participating in the Consortium allows OICR to move forward in its mandate of strengthening Ontario’s cancer research capacity. So far OICR is doing just that, through its different programs, the One Millimetre Challenge, its cohort studies and now as part of the ICGC.

And the main reason to pursue these goals stated Hudson, is simply the terrible toll cancer is inflicting on humankind. It is estimated that in 2007 over 12 million new cases were diagnosed across the globe and 7.6 million cancer deaths occurred. It is also now the leading cause of death in Canada. As such, he feels the time for a systematic, collaborative and comprehensive exploration of the genomics of cancer has been long overdue and while the ICGC generally has lofty goals, they are goals that can be realized mainly because technology in the field of genomics has drastically improved.

“What we’re trying to accomplish with the ICGC is really driven by technology. Cancer is a disease driven by mutation and there’s hundreds and thousands of mutations in every cancer. In the past we had no way to cope with all this data and to identify all these mutations but with next generation sequencing and technology that is hundreds of times faster than the old machines at the big genome centres, we now have the ability to look at the whole genome of cancer for relatively low cost and we anticipate that the cost will continue to decrease,” he stated.

Hudson also believes international cooperation is essential to maximize opportunities and pivotal to achieving the goals of this project because of the large numbers of tumours that need to be looked at and the burden of cancer is different in different parts of the world. Just doing it one place would give only a partial picture of different types of cancer.

“This is a chance for cancer researchers around the world to collaborate, not compete. Even with great technologies we realized there are many types of cancer and systematically we need to look at lots of samples, and the consortia model is the right way of approaching it. No one organization can unilaterally deal with all this information we hope to generate,” he said.

The stated goal of 50 ICGC projects is not intended to, and cannot, exhaustively cover the full spectrum of cancer types. That is why Hudson hopes more will come on board.

“It is hoped that eventually other Canadian cancer and genomics institutes will join the consortium, (we’ve only identified about 10 groups to do the first 50). The need is there and OICR would like to have the opportunity to participate in other projects but whether more Canadian projects are undertaken will depend on finding other sources of funding, such as the federal or provincial governments,” said Hudson.

According to Hudson, the centre with the longest track record in genomics and cancer in Canada is the BC Cancer Agency, and obviously it wants to participate in the Consortium.

“We’re working together to raise awareness on the federal level and obviously he’s (Dr. Marco Marra, BC Cancer Agency Genome Sciences Centre) trying to raise awareness at the provincial level. I’ve talked to at least 10 cancer funding agencies across the country and many of them are showing interest. Until the Goals, Structure, Policies and Guidelines paper was out it was very hard to get commitments, but certainly the awareness now with the information on this consortium out there and now these agencies across the country know what they can contribute, many of them can’t contribute $20 million to a whole project but we’re hoping to create some alliances of different funding sources to fund other projects,” said Hudson.

In addition to its role as hosting the secretariat and main database, OICR is tackling one of the deadliest types of cancer in terms of survival rates, pancreatic cancer. Dr. Tom Hudson along with Dr. John McPherson, director of the OICR Cancer Genome Program are developing a plan for OICR to tackle this cancer type in conjunction with leading pancreatic cancer clinicians in Toronto and internationally.

As part of this effort, a ‘Next Generation’ sequencing team has been trained and is ramping up capacity to read 60 billion DNA bases per week. In comparison, large-scale genome centres using traditional fluorescent-based capillary sequencers produce about 1.25-2.5 billion DNA bases per week.

Hudson explains the decision to target this cancer was influenced by Ontario’s reputation in the field, strengths in terms of its local researchers, pathologists, surgeons and other collaborators.

According to Hudson the hierarchy of the ICGC will work through consensus, there are no leaders.

“We are responsible for producing data in our own jurisdictions and you won’t see one country tell another country how to do things. What we look more for is consensus decisions at the level of governance and then the funders make sure that information is translated to the scientists and back and forth such that we are all aligned,” he stated.

The coordination of who’s doing what will be handled by the secretariat that will be hosted at OICR. In addition to this responsibility the institute will also host the data centre to catalogue research and disseminate it to teams within the consortium, confirm its accuracy and then release it to the public.

ICGC members will assume responsibility for specific cancers and study the genomic changes in those cancers through efforts that may require up to a decade.

All consortium participants will agree not to file any patent applications or make other intellectual property claims on primary data from ICGC projects. The ICGC’s main criteria for prioritizing cancer types are: impact, including incidence and mortality rates, age of onset and availability of therapies; scientific interest and feasibility, including the ability to obtain enough high-quality samples to conduct a large-scale project.

Following the lead of the Human Genome project, all data generated from the consortium will be made freely available to the worldwide research community.

“Every night we’ll go and get the data that was deposited at the franchise databases at the partner centres, check it for content, what progress has been made, do some quality control checks and then release it through public websites where the data will go out to the science community.”

Adds Hudson, there will be two levels to accessing this information, one called open access, the other controlled access.

“The open access is pretty simple like all the mutations, the names of the mutations and so on are just put out as soon as they’re released on public websites here, but they’re also sent out to Genbank and others. Controlled access has very detailed information that can be used or misused on individuals who participate in the studies.
The controlled access ensures us of a way of making sure that the patients are protected from someone misusing their data. There’s very detailed information in there, even if you don’t have their names, three billion bases of DNA sequence is a lot of information.”

Overall the benefits to both participating in and hosting this huge global effort for Ontario are numerous. As Hudson explains other projects in Ontario will also benefit from having access to these cutting edge technologies and databases.

“We hope to have a synergistic effect, great science, additional funding, programs that link together diverse groups including clinicians is going to propel the science towards translation.”

Others such as the Minister of Research and Innovation, John Wilkinson, are equally excited go so far as is to say that this project could mean to Toronto biotech what the Human Genome project meant to Boston.

There are many that hope both men are right.