Large study of whole genome sequencing data reveals 'treasure trove' of
clues about causes of cancer

Date:
April 21, 2022
Source:
University of Cambridge
Summary:
DNA analysis of thousands of tumours from patients has found a
'treasure trove' of clues about the causes of cancer, with genetic
mutations providing a personal history of the damage and repair
processes each patient has been through.



FULL STORY ==========================================================================
DNA analysis of thousands of tumours from NHS patients has found a
'treasure trove' of clues about the causes of cancer, with genetic
mutations providing a personal history of the damage and repair processes
each patient has been through.


==========================================================================
In the biggest study of its kind, a team of scientists led by Professor
Serena Nik-Zainal from Cambridge University Hospitals (CUH) and University
of Cambridge, analysed the complete genetic make-up or whole-genome
sequences of more than 12,000 NHS cancer patients.

Because of the vast amount of data provided by whole genome sequencing,
the researchers were able to detect patterns in the DNA of cancer -- or 'mutational signatures' -- that provide clues about whether a patient
has had a past exposure to environmental causes of cancer such as smoking
or UV light, or has internal, cellular malfunctions.

The team were also able to spot 58 new mutational signatures, suggesting
that there are additional causes of cancer that we don't yet fully
understand.

This research was supported by Cancer Research UK and published today
in the journal Science. The genomic data were provided by the 100,000
Genomes Project an England-wide clinical research initiative to sequence 100,000 whole genomes from around 85,000 patients affected by rare
disease or cancer.

Dr Andrea Degasperi, research associate at the University of Cambridge
and first author said: "Whole genome sequencing gives us a total
picture of all the mutations that have contributed to each person's
cancer. With thousands of mutations per cancer, we have unprecedented
power to look for commonalities and differences across NHS patients,
and in doing so we uncovered 58 new mutational signatures and broadened
our knowledge of cancer." Serena Nik-Zainal, a professor of genomic
medicine and bioinformatics at the University of Cambridge and an honorary consultant in clinical genetics at CUH said: "The reason it is important
to identify mutational signatures is because they are like fingerprints
at a crime scene -- they help to pinpoint cancer culprits. Some mutational signatures have clinical or treatment implications - - they can highlight abnormalities that may be targeted with specific drugs or may indicate
a potential 'Achilles heel' in individual cancers.

"We were able to perform a forensic analysis of over 12,000 NHS
cancer genomes thanks to the generous contribution of samples from
patients and clinicians throughout England. We have also created FitMS,
a computer-based tool to help scientists and clinicians identify old
and new mutational signatures in cancer patients, to potentially inform
cancer management more effectively." Michelle Mitchell, chief executive
of Cancer Research UK, said: "This study shows how powerful whole genome sequencing tests can be in giving clues into how the cancer may have
developed, how it will behave and what treatment options would work
best. It is fantastic that insight gained through the NHS 100,000 Genomes Project can potentially be used within the NHS to improve the treatment
and care for people with cancer." Professor Matt Brown, chief scientific officer of Genomics England said: "Mutational signatures are an example of using the full potential of WGS. We hope to use the mutational clues seen
in this study and apply them back into our patient population, with the ultimate aim of improving diagnosis and management of cancer patients."

========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
text of this story is licensed under a Creative_Commons_License. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Andrea Degasperi, Xueqing Zou, Tauanne Dias Amarante, Andrea
Martinez-
Martinez, Gene Ching Chiek Koh, Joa~o M. L. Dias, Laura Heskin,
Lucia Chmelova, Giuseppe Rinaldi, Valerie Ya Wen Wang, Arjun
S. Nanda, Aaron Bernstein, Sophie E. Momen, Jamie Young, Daniel
Perez-Gil, Yasin Memari, Cherif Badja, Scott Shooter, Jan Czarnecki,
Matthew A. Brown, Helen R.

Davies, Serena Nik-Zainal, J. C. Ambrose, P. Arumugam, R. Bevers, M.

Bleda, F. Boardman-Pretty, C. R. Boustred, H. Brittain,
M. J. Caulfield, G. C. Chan, T. Fowler, A. Giess, A. Hamblin,
S. Henderson, T. J. P.

Hubbard, R. Jackson, L. J. Jones, D. Kasperaviciute, M. Kayikci, A.

Kousathanas, L. Lahnstein, S. E. A. Leigh, I. U. S. Leong,
F. J. Lopez, F. Maleady-Crowe, M. McEntagart, F. Minneci,
L. Moutsianas, M. Mueller, N. Murugaesu, A. C. Need, P. O`Donovan,
C. A. Odhams, C. Patch, D. Perez- Gil, M. B. Pereira, J. Pullinger,
T. Rahim, A. Rendon, T. Rogers, K.

Savage, K. Sawant, R. H. Scott, A. Siddiq, A. Sieghart, S. C. Smith,
A.

Sosinsky, A. Stuckey, M. Tanguy, A. L. Taylor Tavares,
E. R. A. Thomas, S. R. Thompson, A. Tucci, M. J. Welland,
E. Williams, K. Witkowska, S. M.

Wood. Substitution mutational signatures in whole-genome-sequenced
cancers in the UK population. Science, 2022; 376 (6591) DOI:
10.1126/ science.abl9283 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220421141552.htm

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