Next Article in Journal
Lung Cancer Screening, towards a Multidimensional Approach: Why and How?
Next Article in Special Issue
Reverse Engineering Cancer: Inferring Transcriptional Gene Signatures from Copy Number Aberrations with ICAro
Previous Article in Journal
TARBP2-Enhanced Resistance during Tamoxifen Treatment in Breast Cancer
Previous Article in Special Issue
Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer: A Study from Databases to AI-Assisted Verification
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle

Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes

1
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894-6075, USA
2
Center for Collaborative Research in Health Disparities–RCMI Program, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936, USA
3
Department Microbiology and Molecular Genetics, University of California, Davis, CA 95616, USA
4
Institute of Cytology and Genetics, Novosibirsk 630090, Russia
5
Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
6
Institute of Medical Genetics, Cardiff University, Cardiff CF14 4AY, UK
7
Departments of Microbiology and Pathology; Biochemistry and Molecular Biology; Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA
8
Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68198, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2019, 11(2), 211; https://doi.org/10.3390/cancers11020211
Received: 11 January 2019 / Revised: 30 January 2019 / Accepted: 30 January 2019 / Published: 12 February 2019
(This article belongs to the Special Issue Application of Bioinformatics in Cancers)
  |  
PDF [1385 KB, uploaded 25 February 2019]
  |  

Abstract

Cancer genomes accumulate nucleotide sequence variations that number in the tens of thousands per genome. A prominent fraction of these mutations is thought to arise as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases. These enzymes, collectively called activation induced deaminase (AID)/APOBECs, deaminate cytosines located within defined DNA sequence contexts. The resulting changes of the original C:G pair in these contexts (mutational signatures) provide indirect evidence for the participation of specific cytosine deaminases in a given cancer type. The conventional method used for the analysis of mutable motifs is the consensus approach. Here, for the first time, we have adopted the frequently used weight matrix (sequence profile) approach for the analysis of mutagenesis and provide evidence for this method being a more precise descriptor of mutations than the sequence consensus approach. We confirm that while mutational footprints of APOBEC1, APOBEC3A, APOBEC3B, and APOBEC3G are prominent in many cancers, mutable motifs characteristic of the action of the humoral immune response somatic hypermutation enzyme, AID, are the most widespread feature of somatic mutation spectra attributable to deaminases in cancer genomes. Overall, the weight matrix approach reveals that somatic mutations are significantly associated with at least one AID/APOBEC mutable motif in all studied cancers. View Full-Text
Keywords: DNA sequence profile; Monte Carlo; mixture of normal distributions; somatic mutation; tumor; mutable motif; activation induced deaminase; AID/APOBEC DNA sequence profile; Monte Carlo; mixture of normal distributions; somatic mutation; tumor; mutable motif; activation induced deaminase; AID/APOBEC
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Rogozin, I.B.; Roche-Lima, A.; Lada, A.G.; Belinky, F.; Sidorenko, I.A.; Glazko, G.V.; Babenko, V.N.; Cooper, D.N.; Pavlov, Y.I. Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes. Cancers 2019, 11, 211.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top