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

An international team, including researchers at the Big Data Institute, 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; 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.

David Wedge, a group leader at the BDI, co-led the Evolution and Heterogeneity Working Group of the PCAWG project, said, 'This study identified a small number of mutations that cause initial tumour growth and a much larger range of mutations, with different characteristics, that are associated with later tumour growth. Mutations that drive tumour growth had occurred in many cancers as much as 20 years or more before diagnosis, suggesting that there may be opportunities for earlier detection of many types of cancer.'

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