February 5, 2020

Unprecedented exploration generates most comprehensive map of cancer genomes charted to date

Pan-Cancer Project discovers causes of previously unexplained cancers, pinpoints cancer-causing events and zeroes in on mechanisms of development 

Toronto – (February 5, 2020) An international team has completed the most comprehensive study of whole cancer genomes to date, significantly improving our fundamental understanding of cancer and signposting new directions for its diagnosis and treatment.

The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Project (PCAWG), known as the Pan-Cancer Project, a collaboration involving more than 1,300 scientists and clinicians from 37 countries, analyzed more than 2,600 genomes of 38 different tumour types, creating a huge resource of primary cancer genomes. This was then the launch-point for 16 working groups studying multiple aspects of cancer’s development, causation, progression and classification. 

Previous studies focused on the 1 per cent of the genome that codes for proteins, analogous to mapping the coasts of the continents. The Pan-Cancer Project explored in considerably greater detail the remaining 99 per cent of the genome, including key regions that control switching genes on and off — analogous to mapping the interiors of continents versus just their coastlines.

The Pan-Cancer Project has made available a comprehensive resource for cancer genomics research, including the raw genome sequencing data, software for cancer genome analysis, and multiple interactive websites exploring various aspects of the Pan-Cancer Project data.

The Pan-Cancer Project extended and advanced methods for analyzing cancer genomes which included cloud computing, and by applying these methods to its large dataset, discovered new knowledge about cancer biology and confirmed important findings of previous studies. In 23 papers published today in Nature and its affiliated journals, the Pan-Cancer Project reports that:

  • The cancer genome is finite and knowable, but enormously complicated. By combining sequencing of the whole cancer genome with a suite of analysis tools, we can characterize every genetic change found in a cancer, all the processes that have generated those mutations, and even the order of key events during a cancer’s life history.
  • Researchers are close to cataloguing all of the biological pathways involved in cancer and having a fuller picture of their actions in the genome. At least one causal mutation was found in virtually all of the cancers analyzed and the processes that generate mutations were found to be hugely diverse — from changes in single DNA letters to the reorganization of whole chromosomes. Multiple novel regions of the genome controlling how genes switch on and off were identified as targets of cancer-causing mutations.
  • Through a new method of “carbon dating, Pan-Cancer researchers discovered that it is possible to identify mutations which occurred years, sometimes even decades, before the tumour appears. This opens, theoretically, a window of opportunity for early cancer detection. 
  • Tumour types can be identified accurately according to the patterns of genetic changes seen throughout the genome, potentially aiding the diagnosis of a patient’s cancer where conventional clinical tests could not identify its type. Knowledge of the exact tumour type could also help tailor treatments.

“The incredible work of the Pan-Cancer Project team that was unveiled today is the culmination of a remarkable international collaboration that has enriched our understanding and provided new ways to approach the prevention, diagnosis and treatment of cancer,” said The Honourable Ross Romano, Ontario’s Minister of Colleges and Universities. “I congratulate the entire research group on this ground-breaking achievement in cancer research. Ontarians can be proud of the leading role OICR played in this initiative.”

“The findings we have shared with the world today are the culmination of an unparalleled, decade-long collaboration that explored the entire cancer genome,” says Dr. Lincoln Stein, member of the Project steering committee and Head of Adaptive Oncology at the Ontario Institute for Cancer Research (OICR). “With the knowledge we have gained about the origins and evolution of tumours, we can develop new tools to detect cancer earlier, develop more targeted therapies and treat patients more successfully.”

“The Pan-Cancer Project has generated a much-needed deeper understanding of the biology of cancer and how the elusive and untapped “dark matter” in the human genome drives cancer,” says Dr. Laszlo Radvanyi, OICR’s President and Scientific Director. “These discoveries can lead to totally new area of targets for cancer therapy. It is gratifying to know that OICR helped to lead the international effort, while also integrating a collaborative network of Ontario researchers to play a leading role in this global project. It is a further indication of the value of our strategic investments into data infrastructure, research and informatics expertise, as well as the value the Ontario government continues to create in supporting OICR. I congratulate Dr. Stein, his team and all Pan-Cancer researchers on this landmark achievement.”

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Backgrounder

More information

Nature landing page – https://www.nature.com/collections/pcawg/
ICGC – International Cancer Genome Consortium (https://icgc.org/)
TCGA – The Cancer Genome Atlas (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga)
PCAWG – PanCancer Analysis of Whole Genomes (dcc.icgc.org/pcawg)
UCSC – University of California Santa Cruz (pcawg.xenahubs.net)
Expression Atlas (www.ebi.ac.uk/gxa/home)
PCAWG-Scout (pcawgscout.bsc.es)
Chromothripsis Explorer (compbio.med.harvard.edu/chromothripsis)
COSMIC – Catalogue of Somatic Mutations in Cancer (https://cancer.sanger.ac.uk/cosmic)

About the Ontario Institute for Cancer Research

OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit www.oicr.on.ca.

Media contact

Hal Costie
Ontario Institute for Cancer Research
647-260-7921
hal.costie@oicr.on.ca


Related links

October 9, 2019

Researchers discover a new cancer-driving mutation in the “dark matter” of the cancer genome

Change in just one letter of DNA code in a gene conserved through generations of evolution can cause multiple types of cancer

Toronto – (October 9, 2019) An Ontario-led research group has discovered a novel cancer-driving mutation in the vast non-coding regions of the human cancer genome, also known as the “dark matter” of human cancer DNA.

The mutation, as described in two related studies published in Nature on October 9, 2019, represents a new potential therapeutic target for several types of cancer including brain, liver and blood cancer. This target could be used to develop novel treatments for patients with these difficult-to-treat diseases.

“Non-coding DNA, which makes up 98 per cent of the genome, is notoriously difficult to study and is often overlooked since it does not code for proteins,” says Dr. Lincoln Stein, co-lead of the studies and Head of Adaptive Oncology at the Ontario Institute for Cancer Research (OICR). “By carefully analyzing these regions, we have discovered a change in one letter of the DNA code that can drive multiple types of cancer. In turn, we’ve found a new cancer mechanism that we can target to tackle the disease.”

Continue reading – Researchers discover a new cancer-driving mutation in the “dark matter” of the cancer genome

September 20, 2019

Harnessing the time before a patient’s surgery to accelerate cancer research

Ottawa cancer researchers and clinicians embrace the window of opportunity between a cancer diagnosis and treatment with a coordinated approach to clinical research

The time between a patient’s cancer diagnosis and their surgery presents a valuable “window of opportunity” to evaluate new treatment strategies. Short-term clinical trials during this period – also known as window of opportunity trials, window trials or phase 0 trials – can help researchers gain insights into the effects and the efficacy of a new potential treatment. Dr. Angel Arnaout at The Ottawa Hospital is putting window trials into practice.

“There are many nervous and anxious moments between diagnosis and their surgery but patients have limited options during this time,” says Arnaout.

“We saw an opportunity in this window of time to take action. We saw that we could help support patients who are waiting for surgery, while helping future patients through accelerating clinical research.”

Dr. Angel Arnaout

Arnaout, a surgical oncologist who specializes in breast cancers, assembled a cross-disciplinary team of medical oncologists, pathologists and other clinical research specialists at The Ottawa Hospital to strategically design and implement this new approach. They would collectively establish common priorities, decide on which interventions would be tested and work to streamline the patient’s journey throughout the process.

Dr. Angel Arnaout

Together, the team was motivated by the mutual benefits of all stakeholders involved. Namely, window trials can provide patients an opportunity to contribute and engage with cancer research while potentially improving the state of a patient’s disease. Meanwhile, these trials could ultimately expedite drug development by improving the understanding of a potential drug early in its development.

The team launched their first study in 2014, which found that patients were exceptionally eager to participate, and since then, launched and completed three additional window trials.

The first was a breast cancer trial on presurgical hormone therapy that helped establish the capacity and infrastructure for enrolling patients, organizing the investigations and giving patients short-term therapies. The second tested a potential cancer-fighting agent, chloroquine, and found that it had no effect on stopping breast cancer proliferation. The third trial debunked the idea that vitamin D – even at very high doses – can slow down the growth of breast cancer.

“These studies didn’t uncover a new therapy, but they did help us answer important questions that patients have, like ‘Will taking vitamin D help?’” says Arnaout. “These types of studies also provide a relatively quick method to test whether we should continue research into a particular avenue.”

The group at The Ottawa Hospital has recently teamed up with researchers from OICR to initiate a new breast cancer window-of-opportunity study to examine biomarkers of efficacy and resistance for another new drug candidate. The trial is planned to begin recruitment by mid-fall this year.*

Despite the benefits of these trials, Arnaout adds, it is still important to reduce unnecessary delays between diagnosis and surgery. Arnaout continues to minimize these delays at The Ottawa Hospital.

“We try our best to reduce wait times, but if patients have to wait – we can try to help them in the meantime while accelerating breast cancer research.”

*This new trial is co-led by Dr. John Hilton from The Ottawa Hospital and Dr. John Bartlett from OICR. Co-investigators include Drs. Laszlo Radvanyi, Melanie Spears, Arif Ali Awan, Mark Clemons, Greg Pond and Angel Arnaout.

July 3, 2019

Five fellows, four labs, three years, two countries, and a generous donation

Joesph Lebovic and the fellows


The Lebovic Fellowship program connects scientists in Israel and Ontario, leading to the validation of a new drug candidate for leukemia and the optimization of a new potential cancer vaccine

Three years ago, the Institute for Medical Research Israel-Canada (IMRIC) received a donation from Joseph and Wolf Lebovic – two brothers who are Holocaust survivors, Canadian immigrants, avid philanthropists and recently-appointed Members of the Order of Canada. Their vision was to strengthen collaboration between the outstanding researchers in Israel and those in Ontario to accelerate cancer research.

They created the Joseph and Wolf Lebovic Fellowship Program, which paired together laboratories specializing in complementary subjects. The Program’s first round of projects officially came to a successful close today and here we recognize the progress made thanks to the generous donation of the Lebovic brothers.

Developing a drug for leukemia

Israel lead researcher: Dr. Yinon Ben-Neriah, IMRIC
Israel fellows: Waleed Minzel and Eric Hung, PhD Candidates, Hebrew University of Jerusalem

Ontario lead researcher: Dr. John Dick, Princess Margaret Cancer Centre (PMCC)
Ontario fellow: Dr. Laura Garcia-Prat, Postdoctoral Fellow, PMCC

Ben-Neriah’s lab in Israel had developed a new compound and showed it may be a valuable anti-leukemia drug, but they couldn’t explain why the drug was only effective in animal models that had strong immune systems. Understanding the relationship between the drug and the immune system would allow them to validate which leukemia subtypes would respond to their therapeutic approach.

John Dick’s lab had developed the gold standard for evaluating the efficacy of leukemia drugs in animal models using sophisticated patient-derived xenograft mouse models. Through this fellowship, the Ben-Neriah Lab teamed up with the Dick lab to learn from their expertise and gain insights into their experimental models.

Continue reading – Five fellows, four labs, three years, two countries, and a generous donation

December 10, 2018

A holiday message from the President and Scientific Director

As we approach the holidays, I want to wish you all the best of the season. The remarkable achievements of OICR and the cancer research community over the last year would not have been possible without your dedication, support and collaborative spirit. Together we are continuing to make OICR a huge success with tangible impacts on the lives of cancer patients across the province.

Continue reading – A holiday message from the President and Scientific Director

October 23, 2018

Updates and highlights from Global Alliance’s 6th Plenary Meeting

The Global Alliance for Genomics and Health (GA4GH) held its 6th Plenary Meeting in Basel, Switzerland earlier this month. The meeting brought together more than 430 participants from 25 countries, making it the biggest GA4GH event yet. Attendees of the meeting learned about GA4GH Connect – a strategic phase focused on connecting GA4GH development work to the immediate data sharing needs of the community.

Peter Goodhand, CEO of GA4GH, introducing GA4GH Connect

At the meeting, Peter Goodhand, Chief Executive Officer of GA4GH, announced a call for new real-world genomic data initiatives – Driver Projects – with a specific focus on global collaboration and scientific merit. The Steering Committee will announce the accepted Driver Projects in February 2019.

Also at the meeting, Dr. Marc Fiume, Chief Executive Officer of DNAstack and OICR Associate, presented on the recent progress of the Beacon Project – an international collaborative initiative that has developed a realtime discovery platform for genetic mutations. The Beacon Project has released Beacon API V1.0.0 on Friday – the first genomic data interoperability standard from the GA4GH 2018 Strategic Roadmap.

“It was a fantastic meeting and an eye-opening experience to learn about how the field of precision medicine is linking genomic tools with clinical databases and patient outcomes to drive a patient-centered, learning healthcare model,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “GA4GH continues to play a critical role in establishing standards for genomic data acquisition, quality, interpretation, integrity, security, and sharing that many national genomic health initiatives are beginning to embrace around the world.”

Access highlights and updates from the Plenary Meeting online, or read a PDF of the meeting report here.

June 14, 2018

New OICR President and Scientific Director comments on breakthrough in breast cancer T-cell immunotherapy

Dr. Laszlo Radvanyi

For the first time, a patient’s late-stage breast cancer has been successfully treated with T-cell immunotherapy. This cutting-edge approach, which is currently in clinical trials in the U.S., modified the patient’s naturally-occurring immune cells to fight her tumours that had spread throughout her body. The patient has been cancer free for the past two years and her remarkable tumour regression represents the potential impact of this new immunotherapeutic approach.

Continue reading – New OICR President and Scientific Director comments on breakthrough in breast cancer T-cell immunotherapy

May 1, 2018

Ontario Institute for Cancer Research welcomes new President and Scientific Director, Dr. Laszlo Radvanyi

Dr. Laszlo Radvanyi

Toronto (May 1, 2018) – Mr. Tom Closson, Chair of the Ontario Institute for Cancer Research’s (OICR) Board of Directors, today welcomed to the Institute Dr. Laszlo Radvanyi, OICR’s new President and Scientific Director. Radvanyi was selected after an extensive international search and has extensive oncology-related experience from his time spent in industry, with a particular focus in immuno-oncology. Radvanyi will work with the Ontario cancer research community, and OICR’s commercialization partner FACIT, to see that Ontario’s best innovations are reaching cancer patients as quickly as possible.

Radvanyi joins OICR from EMD Serono (Merck KGaA, Darmstadt Germany), where he was a Senior Vice President, Global Senior Scientific Advisor in Immunology and Immuno-Oncology. There he played a central scientific advisory role, facilitating major academic centre alliances and ran EMD Serono’s CAR T-cell program, in partnership with Intrexon. He also served as Global Head of the Immuno-Oncology Translational Innovation Platform, where he was instrumental in rebuilding immuno-oncology research at the company, hiring new world-class scientific staff, as well as pruning and re-orienting the discovery pipeline.

Continue reading – Ontario Institute for Cancer Research welcomes new President and Scientific Director, Dr. Laszlo Radvanyi

March 28, 2018

OICR names Dr. Laszlo Radvanyi as new President and Scientific Director

 

A photo of the MaRS Centre with an inset photo of Dr. Laszlo Radvanyi

Following an extensive international search, I am very pleased to announce on behalf of the Board of Directors the appointment of Dr. Laszlo Radvanyi as the new President and Scientific Director of the Ontario Institute for Cancer Research (OICR) effective May 1, 2018. Dr. Radvanyi was born and raised in Toronto and obtained his PhD in Clinical Biochemistry from the University of Toronto in 1996. After obtaining his PhD, he performed post-doctoral work at Harvard University (Joslin Diabetes Center) and then worked for four years at Sanofi Pasteur Canada as a Senior Scientist in the Immunology Platform. Dr. Radvanyi brings a strong oncology research background as well as leadership experience in international pharma and small biotech. We are pleased to welcome him back to Ontario.

Dr. Radvanyi has joined OICR from EMD Serono (Merck KGaA, Darmstadt Germany) where he was a Senior Vice President, Global Senior Scientific Advisor in Immunology and Immuno-Oncology playing a central scientific advisory role, facilitating major academic center alliances, and running EMD Serono’s CAR T-cell program in partnership with Intrexon. He also served as Global Head of the Immuno-Oncology Translational Innovation Platform where he was instrumental in rebuilding immuno-oncology research at the company, hiring new world-class scientific staff as well as pruning and re-orienting the discovery pipeline.

Continue reading – OICR names Dr. Laszlo Radvanyi as new President and Scientific Director