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An overview of mutational and copy number signatures in human cancer
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, th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324981/ https://www.ncbi.nlm.nih.gov/pubmed/35420163 http://dx.doi.org/10.1002/path.5912 |
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author | Steele, Christopher D Pillay, Nischalan Alexandrov, Ludmil B |
author_facet | Steele, Christopher D Pillay, Nischalan Alexandrov, Ludmil B |
author_sort | Steele, Christopher D |
collection | PubMed |
description | 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 (1) single base substitutions, (2) doublet base substitutions, and (3) 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 (CN) alterations (CNAs) or even to structural rearrangements. These aberrations also leave behind genomic scars which can be inferred from sequencing as CN signatures and rearrangement signatures. The analyses of mutational signatures of small mutational events have been extensively reviewed, so we will not comprehensively re‐examine them here. Rather, our focus will be on summarising the existing knowledge for mutational signatures of CNAs. As studying CN signatures is an emerging field, we briefly summarise the utility that mutational signatures of small mutational events have provided in basic science, cancer treatment, and cancer prevention, and we emphasise the future role that CN signatures may play in each of these fields. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. |
format | Online Article Text |
id | pubmed-9324981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-93249812022-07-30 An overview of mutational and copy number signatures in human cancer Steele, Christopher D Pillay, Nischalan Alexandrov, Ludmil B J Pathol Invited Reviews 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 (1) single base substitutions, (2) doublet base substitutions, and (3) 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 (CN) alterations (CNAs) or even to structural rearrangements. These aberrations also leave behind genomic scars which can be inferred from sequencing as CN signatures and rearrangement signatures. The analyses of mutational signatures of small mutational events have been extensively reviewed, so we will not comprehensively re‐examine them here. Rather, our focus will be on summarising the existing knowledge for mutational signatures of CNAs. As studying CN signatures is an emerging field, we briefly summarise the utility that mutational signatures of small mutational events have provided in basic science, cancer treatment, and cancer prevention, and we emphasise the future role that CN signatures may play in each of these fields. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. John Wiley & Sons, Ltd 2022-05-20 2022-07 /pmc/articles/PMC9324981/ /pubmed/35420163 http://dx.doi.org/10.1002/path.5912 Text en © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Invited Reviews Steele, Christopher D Pillay, Nischalan Alexandrov, Ludmil B An overview of mutational and copy number signatures in human cancer |
title | An overview of mutational and copy number signatures in human cancer |
title_full | An overview of mutational and copy number signatures in human cancer |
title_fullStr | An overview of mutational and copy number signatures in human cancer |
title_full_unstemmed | An overview of mutational and copy number signatures in human cancer |
title_short | An overview of mutational and copy number signatures in human cancer |
title_sort | overview of mutational and copy number signatures in human cancer |
topic | Invited Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324981/ https://www.ncbi.nlm.nih.gov/pubmed/35420163 http://dx.doi.org/10.1002/path.5912 |
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