Causes of cancer are being catalogued by a huge international study
revealing the genetic fingerprints of DNA-damaging processes that drive cancer
development. Researchers from the Wellcome Sanger Institute, Duke-NUS Medical
School Singapore, University of California San Diego School of Medicine, the
Broad Institute of MIT and Harvard and their collaborators around the world
have achieved the most detailed list of these genetic fingerprints to date,
providing clues as to how each cancer developed.
These fingerprints
will allow scientists to search for previously unknown chemicals, biological
pathways and environmental agents responsible for causing cancer.
The research, published in Nature today (5th February)
as part of a global Pan-Cancer Project, will help understand the causes of
cancer, informing prevention strategies, and help signpost new directions for
cancer diagnosis and treatments.
Also published in Nature and related journals,
are 22 further studies from the Pan-Cancer Project. The collaboration involving
more than 1,300 scientists and clinicians from 37 countries, analysed more than
2,600 genomes of 38 different tumor types. The project represents an
unprecedented international exploration of cancer genomes, which significantly
improves our fundamental understanding of cancer and zeros-in on mechanisms of
cancer development.
In the UK,
someone is diagnosed with cancer every two minutes, with 363,000 new cancer
cases every year. The disease causes around 165,000 deaths in the UK annually.
Cancer is caused
by genetic changes — mutations — in the DNA of a cell, allowing the cell to
divide uncontrollably. Many known causes of cancer, such as UV light and
tobacco smoking, leave a specific fingerprint of damage in the DNA, known as a
mutational signature. These fingerprints can help understand how cancers
develop, and potentially, how they can be prevented. However, past studies have
not been large enough to identify all potential mutational signatures.
The fingerprint
study identified new mutational signatures that had not been seen before, from
single letter ‘typo’ mutations, to slightly larger insertions and deletions of
genetic code. The result is the largest database of reference mutational
signatures ever. Only about half of all the mutational signatures have known
causes, however this resource can now be used to help find more of these causes
and better understand cancer development.
Professor Steven
Rozen, a senior author from Duke-NUS Medical School, Singapore, said: “Some
types of these DNA fingerprints, or mutational signatures, reflect how the
cancer could respond to drugs. Further research into this could help to
diagnose some cancers and what drugs they might respond to.”
Professor Gad
Getz, a senior author from the Broad Institute of MIT and Harvard, and
Massachusetts General Hospital, said, “The availability of a large number of
whole genomes enabled us to apply more advanced analytical methods to discover
and refine mutational signatures and expand our study into additional types of
mutations. Our new collection of signatures provides a more complete picture of
biological and chemical processes that damage or repair DNA and will enable
researchers to decipher the mutational processes that affect the genomes of
newly sequenced cancers.”
Another study in the Pan-Cancer Project, published in Nature today,
discovered that larger, more complex genetic changes that rearrange the DNA
could also act as mutational signatures, and point towards causes of cancer.
Researchers from the Wellcome Sanger Institute and the Broad Institute of MIT
and Harvard and their collaborators found 16 of these signatures that spanned
from rearrangements of single genes to entire chromosomes.
The global
Pan-Cancer Project is the largest and most comprehensive study of whole cancer
genomes yet. The collaboration has created a huge resource of primary cancer
genomes, available to researchers worldwide to advance cancer research.
Journal article: https://www.nature.com/articles/s41586-020-1943-3
https://www.nature.com/articles/s41586-019-1913-9
https://www.nature.com/articles/s41586-020-1969-6
https://www.nature.com/articles/s41586-019-1913-9
https://www.nature.com/articles/s41586-020-1969-6
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