Mutational signatures and mutable motifs in cancer genomes

Igor B. Rogozin, Youri I Pavlov, Alexander Goncearenco, Subhajyoti De, Artem G. Lada, Eugenia Poliakov, Anna R. Panchenko, David N. Cooper

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1085-1101
Number of pages17
JournalBriefings in bioinformatics
Volume19
Issue number6
DOIs
StatePublished - May 30 2017

Fingerprint

Mutagens
Tumors
Genes
Genome
Neoplasms
Nucleotides
Mutation
DNA
Repair
Substitution reactions
Enzymes
Chemical activation
Liquids
DNA Repair Enzymes
Inborn Genetic Diseases
Genomics
Tumor Suppressor Genes
Oncogenes
Point Mutation
Germ Cells

Keywords

  • Cancer genomics
  • Classification
  • DNA sequence context
  • Methylation
  • Mutation spectra
  • Somatic hypermutation

ASJC Scopus subject areas

  • Information Systems
  • Molecular Biology

Cite this

Rogozin, I. B., Pavlov, Y. I., Goncearenco, A., De, S., Lada, A. G., Poliakov, E., ... Cooper, D. N. (2017). Mutational signatures and mutable motifs in cancer genomes. Briefings in bioinformatics, 19(6), 1085-1101. https://doi.org/10.1093/bib/bbx049

Mutational signatures and mutable motifs in cancer genomes. / Rogozin, Igor B.; Pavlov, Youri I; Goncearenco, Alexander; De, Subhajyoti; Lada, Artem G.; Poliakov, Eugenia; Panchenko, Anna R.; Cooper, David N.

In: Briefings in bioinformatics, Vol. 19, No. 6, 30.05.2017, p. 1085-1101.

Research output: Contribution to journalArticle

Rogozin, IB, Pavlov, YI, Goncearenco, A, De, S, Lada, AG, Poliakov, E, Panchenko, AR & Cooper, DN 2017, 'Mutational signatures and mutable motifs in cancer genomes', Briefings in bioinformatics, vol. 19, no. 6, pp. 1085-1101. https://doi.org/10.1093/bib/bbx049
Rogozin IB, Pavlov YI, Goncearenco A, De S, Lada AG, Poliakov E et al. Mutational signatures and mutable motifs in cancer genomes. Briefings in bioinformatics. 2017 May 30;19(6):1085-1101. https://doi.org/10.1093/bib/bbx049
Rogozin, Igor B. ; Pavlov, Youri I ; Goncearenco, Alexander ; De, Subhajyoti ; Lada, Artem G. ; Poliakov, Eugenia ; Panchenko, Anna R. ; Cooper, David N. / Mutational signatures and mutable motifs in cancer genomes. In: Briefings in bioinformatics. 2017 ; Vol. 19, No. 6. pp. 1085-1101.
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