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Brief Bioinform. 2018 Nov 27;19(6):1085-1101. doi: 10.1093/bib/bbx049.

Mutational signatures and mutable motifs in cancer genomes.

Author information

1
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, USA.
2
Eppley Institute for Cancer Research, University of Nebraska Medical Center, USA.
3
National Center for Biotechnology Information, National Institutes of Health, USA.
4
Rutgers University Cancer Institute, USA.
5
Department Microbiology and Molecular Genetics, University of California, Davis, USA.
6
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, USA.
7
Institute of Medical Genetics, Cardiff University, UK.

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.

PMID:
28498882
PMCID:
PMC6454500
DOI:
10.1093/bib/bbx049
[Indexed for MEDLINE]
Free PMC Article

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