دورية أكاديمية
Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes.
العنوان: | Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes. |
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المؤلفون: | Rogozin IB; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894-6075, USA. rogozin@ncbi.nlm.nih.gov., Roche-Lima A; Center for Collaborative Research in Health Disparities⁻RCMI Program, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico 00936-5067. abiel.roche@upr.edu., Lada AG; Department Microbiology and Molecular Genetics, University of California, Davis, CA 95616, USA. alada@ucdavis.edu., Belinky F; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894-6075, USA. frida.belinky@gmail.com., Sidorenko IA; Institute of Cytology and Genetics, Novosibirsk 630090, Russia. vanyasidorenko22@gmail.com., Glazko GV; Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. GVGlazko@uams.edu., Babenko VN; Institute of Cytology and Genetics, Novosibirsk 630090, Russia. babenko@yahoo.com., Cooper DN; Institute of Medical Genetics, Cardiff University, Cardiff CF14 4AY, UK. CooperDN@cardiff.ac.uk., Pavlov YI; Departments of Microbiology and Pathology; Biochemistry and Molecular Biology; Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA. ypavlov@unmc.edu.; Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE 68198, USA. ypavlov@unmc.edu. |
المصدر: | Cancers [Cancers (Basel)] 2019 Feb 12; Vol. 11 (2). Date of Electronic Publication: 2019 Feb 12. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
مستخلص: | 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. |
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معلومات مُعتمدة: | U54 MD007600 United States MD NIMHD NIH HHS; Intramural Research Program National Institutes of Health; 2017-48 Nebraska Department of Health and Human Services; 2018-06 Fred and Pamela Buffett Cancer Center; U54 MD007600 National Institute on Minority Health and Health Disparities; P20GM121293 NIH Center for Biomedical Research; P30 CA072720 National Cancer Institute; P20GM103429 NIH INBRE |
فهرسة مساهمة: | Keywords: AID/APOBEC; DNA sequence profile; Monte Carlo; activation induced deaminase; mixture of normal distributions; mutable motif; somatic mutation; tumor |
تواريخ الأحداث: | Date Created: 20190215 Latest Revision: 20200930 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC6406962 |
DOI: | 10.3390/cancers11020211 |
PMID: | 30759888 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2072-6694 |
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DOI: | 10.3390/cancers11020211 |