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An overview of mutational and copy number signatures in human cancer

Steele, Christopher D; Pillay, Nischalan; Alexandrov, Ludmil B; (2022) An overview of mutational and copy number signatures in human cancer. Journal of Pathology 10.1002/path.5912. (In press).

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Abstract

The genome of each cell in the human body is constantly under assault from a plethora of exogenous and endogenous processes that can damage DNA. If not successfully repaired, DNA damage generally becomes permanently imprinted in cells, and all their progenies, as somatic mutations. In most cases, the patterns of these somatic mutations contain the tell-tale signs of the mutagenic processes that have imprinted and are termed mutational signatures. Recent pan-cancer genomic analyses have elucidated the compendium of mutational signatures for all types of small mutational events, including: (i) single base substitutions; (ii) doublet base substitutions; and (iii) small insertions/deletions. In contrast to small mutational events, where, in most cases, DNA damage is a prerequisite, aneuploidy, which refers to the abnormal number of chromosomes in a cell, usually develops from mistakes during DNA replication. Such mistakes include DNA replication stress, mitotic errors caused by faulty microtubule dynamics, or cohesion defects that contribute to chromosomal breakage and can lead to copy number alterations or even to structural rearrangements. These aberrations also leave behind genomic scars which can be inferred from sequencing as copy number signatures and rearrangement signatures. The analyses of mutational signatures of small mutational events have been extensively reviewed [1-3], so we will not comprehensively re-examine them here. Rather, our focus will be on summarizing the existing knowledge for mutational signatures of copy number alterations. As studying copy number signatures is an emerging field, we briefly summarize the utility that mutational signatures of small mutational events have provided in basic science, cancer treatment, and cancer prevention and we emphasize the future role that copy number signatures may play in each of these fields.

Type: Article
Title: An overview of mutational and copy number signatures in human cancer
Location: England
DOI: 10.1002/path.5912
Publisher version: https://doi.org/10.1002/path.5912
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: cancer, copy number signatures, genomics, mutational signatures
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10147099
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