An international team, that includes researchers from McGill, 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 1,300scientists and clinicians from 37 countries, analyzed more than2,600genomes of 38different 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.
Sharing a resource for cancer genomics research
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 23papers published today in Natureand 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 cancerand 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 changesseen 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.
“Such exciting results from a decade of collaboration and data sharing… But is drawing such a map still possible under Europe’s new General Data Protection Regulation? Or, are actual and future patients now protected against themselves, making open scientific resources a thing of the past? The adoption of an international Code of Conduct is needed to mitigate and reduce such emerging barriers in order to continue to foster the mapping of diseases that know no borders,” said Prof. Bartha Maria Knoppers, Director, Centre of Genomics and Policy, McGill University and one of the Co-authors on the study.
To read "Genomics: data sharing needs an international code of conduct" by Mark Phillips et al in Nature: https://www.nature.com/articles/d41586-020-00082-9
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)
Chromothripsis Explorer (compbio.med.harvard.edu/chromothripsis)
About McGill University
Founded in Montreal, Quebec, in 1821, McGill University is Canada’s top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% per cent of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.