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Cited by 58Cancer Genomics and DiagnosticsGenomics and Phylogenetic StudiesChromatin Remodeling and Cancer

Mutational signatures and mutable motifs in cancer genomes

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Rogozin, Igor B., Pavlov, Youri I., Goncearenco, Alexander, De, Subhajyoti, Lada, Artem G., Poliakov, Eugenia, Panchenko, Anna R., Cooper, David N.·2017·Briefings in Bioinformatics
DOI 10.1093/bib/bbx049PMC PMC6454500
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Abstract

Cancer is a genetic disorder, meaning that a plethora of different mutations, whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'. Point mutations, chromosomal rearrangements and copy number changes, whether they have occurred spontaneously in predisposed individuals or have been induced by intrinsic or extrinsic (environmental) mutagens, lead to the activation of oncogenes and inactivation of tumor suppressor genes, thereby promoting malignancy. This scenario has now been recognized and experimentally confirmed in a wide range of different contexts. Over the past decade, a surge in available sequencing technologies has allowed the sequencing of whole genomes from liquid malignancies and solid tumors belonging to different types and stages of cancer, giving birth to the new field of cancer genomics. One of the most striking discoveries has been that cancer genomes are highly enriched with mutations of specific kinds. It has been suggested that these mutations can be classified into 'families' based on their mutational signatures. A mutational signature may be regarded as a type of base substitution (e.g. C:G to T:A) within a particular context of neighboring nucleotide sequence (the bases upstream and/or downstream of the mutation). These mutational signatures, supplemented by mutable motifs (a wider mutational context), promise to help us to understand the nature of the mutational processes that operate during tumor evolution because they represent the footprints of interactions between DNA, mutagens and the enzymes of the repair/replication/modification pathways.

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  • The pol η mutational signature known as Signature 9 occurs in chronic lymphocytic leukemia and malignant B-cell lymphoma genomes.

    “It has also been noted that the 'pol h mutational signature' (Signature 9; http://cancer.sanger.ac.uk/cosmic/sig natures) occurs in chronic lymphocytic leukemia and malignant Bcell lymphoma genomes 6,26,27 .”

    From DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [27]

  • Some endogenous or exogenous mutational mechanisms may have very similar or identical signatures, so a given signature cannot be attributed solely and exclusively to one molecular mechanism.

    “In fact, we can never be sure that a given mutational signature can be attributed solely and exclusively to one molecular mechanismindeed, some endogenous or exogenous mutational mechanisms may have very similar or even identical signatures 27,29 .”

    From DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [27]

  • Signature 9 is characterized by a pattern widely attributed to pol η, although a higher frequency of T:A > G:C transversions compared to T:A > C:G transitions has not been observed in pol η studies in vitro or in vivo.

    “although a higher frequency of T:A > G:C transversions compared to T:A > C:G transitions, has not been observed in studies of pol h either in vitro or in vivo 27,29 .”

    From DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [27]

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Authors
Rogozin, I. B., Pavlov, Y. I., Goncearenco, A., De, S., Lada, A. G., Poliakov, E., Panchenko, A. R., & Cooper, D. N.
Affiliations
  • National Institutes of Health (US)
  • University of Nebraska Medical Center (US)
  • Rutgers, The State University of New Jersey (US)
  • University of California, Davis (US)
  • Cardiff University (GB)
Corresponding author
Rogozin, Igor B.
ORCID
Venue
Briefings in Bioinformatics
Publisher
Oxford University Press (OUP)
Published
2017-05-11
Volume
19
Issue
6
Pages
1085-1101
ISSN
  • 1467-5463 (ISSN-L)
  • 1477-4054
DOI
10.1093/bib/bbx049
PMC
PMC6454500
OpenAlex
W2612847024
Cited by
58
References
12
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FWCI
0.67
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Briefings in Bioinformatics (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Boettcher Foundation (P30 CA072720)
  • Nebraska Department of Health and Human Services
  • Cardiff University
  • National Institutes of Health (CA072720)
  • National Eye Institute
  • National Cancer Institute (P30CA072720)
  • U.S. National Library of Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
mutational signatures, cancer genomics, somatic mutations, mutational processes, mutagen exposure, tumor evolution, copy number alterations, chromosomal rearrangements, point mutations, DNA repair pathways, oncogene activation, tumor suppressor inactivation
MeSH terms
DNA, Humans, Models, Genetic, Mutagens, Mutation, Neoplasms, Oncogenes, Selection, Genetic, Gene Expression, Evolution, Molecular, DNA Methylation, Genetic Predisposition to Disease, Genomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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