Mutational mapmakers chart course to cancer prevention
In this article in Science, learn about how Mutographs fundamentally changed how scientists think about cancer.
The unusual mutation patterns challenge was set in 2015 to discover how unusual patterns of mutation were induced by different cancer-causing agents. It was expected that tackling this challenge would unveil the mechanisms that led from insult to mutation, identifying new prevention targets to stop, delay, or weaken their impact.
Over the past seven years, the Cancer Grand Challenges Mutographs team, funded by Cancer Research UK, has transformed our understanding of the mechanisms of carcinogenesis. The team’s work was underpinned by a strategic alliance with the International Agency for Research in Cancer (WHO-IARC) and the Wellcome Sanger Institute, enabled through their Cancer Grand Challenge award.
The team's seminal discoveries span from identifying unknown mutational signatures and uncovering multiple widespread mutagenic exposures of known and unknown causes, to revealing the complex mutation patterns in healthy tissues, challenging the somatic theory of ageing, as well as adding to the body of evidence for the promotional theory of carcinogenesis.
This was a major shift in how the field thought about how carcinogens cause cancer, highlighting an important role for non-mutagenic carcinogens in human cancer and rejuvenating the idea of cancer promotion in the field. This led to Cancer Grand Challenges setting the Normal Phenotypes challenge, which aimed to identify how cells maintain a normal phenotype despite harbouring oncogenic mutations and what causes them to develop into cancer.
Team Mutographs has pioneered the field of mutational epidemiology, paving the way for potential new approaches to cancer prevention.