The International Cancer Genome Consortium - The Cancer Genome Atlas (ICGC/TCGA) Pan-Cancer Analysis of Whole Genomes Project (PCAWG), known as the Pan-Cancer Project, a collaboration involving more than 1300 scientists and clinicians from 37 countries, analyzed more than 2600 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 cancers development, causation, progression and classification.
Previous studies focused on the 1 percent 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 percent 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.
Among the few data analysis centres around the world involved in the management and analysis of the Pan-Cancer data, BSC has been the most active European supercomputing centre. Already involved in the early stages of this initiative, BSC has had a wide contribution to the project, covering the primary analysis of genomes, including the detection of mutations; the generation of related computing resources; as well as the identification of non-functional gene copies that can have a direct impact on the offset and progression of tumours.
Two genome sequences from each donor - one from a healthy cell and one from a tumour cell - have been analyzed by different methods. With the BWA method, the two genomes of each donor were aligned with the reference human genome. Subsequently, the results of this alignment were analyzed with Sanger, DKFZ / EMBL, Broad / MUSE methods to compare the healthy and tumour genomes of the same patient and to detect possible mutations present in the tumour. In the BSC, 14% of these analyzes were performed. One of the four methods of analysis (Broad / MUSE) has only been performed in the United States due to intellectual property issues in its algorithm.
"Beyond the specific discoveries regarding the biological processes behind the origin and progression of tumours, this effort has resulted in one of the largest international efforts in biomedicine, and has set up the path for future world-wide initiatives in relation to cancer genomics, and for Personalized Medicine in general", stated Dr. David Torrents, ICREA research professor, leading the Computational Genomics groups at the BSC. "This project has placed our center among the top reference centers world-wide for data analysis in biomedicine and, in particular, for genomic oncology."
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 in Nature and its affiliated journals, the Pan-Cancer Project reports that:
"The findings we have shared with the world today are the culmination of an unparalleled, decade-long collaboration that explored the entire cancer genome", stated 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 and therapies to detect cancer earlier, develop more targeted therapies and treat patients more successfully."
"This work is helping to answer a long-standing medical difficulty, why two patients with what appear to be the same cancer can have very different outcomes to the same drug treatment. We show that the reasons for these different behaviours are written in the DNA. The genome of each patient's cancer is unique, but there are a finite set of recurring patterns, so with large enough studies we can identify all these patterns to optimize diagnosis and treatment", stated Dr. Peter Campbell, member of the Pan-Cancer Project steering committee and Head of Cancer, Ageing and Somatic Mutation at the Wellcome Sanger Institute in the UK.
"This study provides the most complete picture to date of cancer-causing mutations in all parts of the genome. It was a massive team science effort involving researchers spanning the globe", stated steering committee member Josh Stuart, a professor of biomolecular engineering at UC Santa Cruz. "At UC Santa Cruz, our strengths in systems biology and RNA expression helped us connect findings in the previously unexplored noncoding genome with the pathways that lead to cancer. Like a charted map, this new work creates a reference and resource that researchers can use to interpret future data and physicians can use to guide treatment."
"With the continuing drop in sequencing costs and accumulation of genomic data across increasing numbers of patients worldwide, the comprehensive analyses performed in this project will serve as a template for future work and will enable new discoveries in cancer", stated steering committee member, Dr. Gad Getz, professor of pathology at the Massachusetts General Hospital and the Broad Institute of MIT and Harvard.
"This huge international study was only possible due to the work and collaboration of more than a thousand researchers and clinicians across the world, and I would like to thank everyone involved", stated steering committee member Dr. Jan Korbel from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany.
"The completion of this project represents the culmination of more than a decade of ground-breaking work in studying the cancer genome", stated Dr. Tom Hudson, Chief Scientific Officer at AbbVie and a founder of the International Cancer Genome Consortium. "When we launched ICGC in 2007, an initiative of this magnitude was unprecedented. I am thrilled that the scientific community has come together to produce this comprehensive study, which enhances our understanding of cancer and fosters the development of new medicines for cancer patients."
"ICGC's latest initiative called 'Accelerating Research in Genomic Oncology' (ARGO) is about the patient, with the goal of delivering to the world 1 million patient-years of precision oncology knowledge to improve human health. This data must be shared across traditional jurisdictional boundaries to realize the full impact of precision medicine, for the benefit of all", stated Andrew Biankin AO, Regius Professor of Surgery and Director of the Wolfson Wohl Cancer Research Centre at the University of Glasgow, and Executive Director, International Cancer Genome Consortium.
"Using the data and infrastructure created by The Cancer Genome Atlas (TCGA) as a blueprint, PCAWG has further improved our understanding of cancer and strengthened our ability to develop successful, international projects of this scale", stated Jean Claude Zenklusen, Ph.D., director of TCGA Programme Office at the National Cancer Institute (NCI). "In addition to benefiting the cancer research field, this collaboration also honors the many patients who donated samples to TCGA - turning their finite gift of tissue into data that can be used infinitely", stated Carolyn Hutter, Ph.D., National Human Genome Research Institute team lead for TCGA.