Cited by 33Cancer Genomics and DiagnosticsLymphoma Diagnosis and TreatmentEpigenetics and DNA Methylation

Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers

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Rogozin, Igor B., Lada, Artem G., Goncearenco, Alexander, Green, Michael R., De, Subhajyoti, Nudelman, German, Panchenko, Anna R., Koonin, Eugene V. +1 more·2016·Scientific Reports

Abstract

Follicular lymphoma (FL) is an uncurable cancer characterized by progressive severity of relapses. We analyzed sequence context specificity of mutations in the B cells from a large cohort of FL patients. We revealed substantial excess of mutations within a novel hybrid nucleotide motif: the signature of somatic hypermutation (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps the CpG methylation site. This finding implies that in FL the SHM machinery acts at genomic sites containing methylated cytosine. We identified the prevalence of this hybrid mutational signature in many other types of human cancer, suggesting that AID-mediated, CpG-methylation dependent mutagenesis is a common feature of tumorigenesis.

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  1. Rogozin I. B. & Kolchanov N. A. Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis. Biochimica et Biophysica Acta 1171, 11– 18 (1992). 1420357
  2. Morgan H. D., Dean W., Coker H. A., Reik W. & Petersen-Mahrt S. K. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. The Journal of Biological Chemistry 279, 52353– 52360 (2004). 15448152

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Authors
Rogozin, I. B., Lada, A. G., Goncearenco, A., Green, M. R., De, S., Nudelman, G., Panchenko, A. R., Koonin, E. V., & Pavlov, Y. I.
Affiliations
  • National Institutes of Health (US)
  • University of Nebraska Medical Center (US)
  • Rutgers, The State University of New Jersey (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
  • Rogozin, Igor B.
  • Pavlov, Youri I.
Venue
Scientific Reports
Published
2016-12-07
Volume
6
Issue
1
Pages
38133-38133
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2559869208
Cited by
33
References
54
Citations by year
2026: 1 · 2024: 5 · 2022: 3 · 2021: 10 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 4
FWCI
1.81
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • U.S. Department of Health and Human Services
  • Saint Petersburg State University (1.38.426.2015)
  • U.S. National Library of Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
follicular lymphoma, activation-induced cytidine deaminase, somatic hypermutation, mutational signatures, CpG methylation, B cells, carcinogenesis
MeSH terms
B-Lymphocytes, Cytosine, Humans, Lymphoma, Follicular, Mutation, Nucleoside Deaminases, Nucleotides, Mutagenesis, CpG Islands, DNA Methylation, Carcinogenesis

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