Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers
Open accessAbstract
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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In follicular lymphoma, the pol η WA/TW signature was significant only in 5'UTR regions (P = 0.01).
“Previously, we found a signature of pol h (WA/TW) in follicular lymphoma which was significant only in 5'UTR regions (P-value = 0.01) 36 .”
From DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [36]
DNA polymerase η is thought to scan a limited length of DNA to mutate nucleotides in a preferred motif.
“pol h is thought to scan a limited length of DNA to mutate nucleotides in a preferred motif 36,54 .”
From DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [36]
The approach of comparing mutable motif frequencies in mutation locations to those in the DNA neighborhood was thoroughly tested and demonstrated high accuracy.
“This approach was thoroughly tested and its high accuracy demonstrated 36 .”
From DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer (2018) · cites this paper as [36]
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DNA polymerase <b>η</b> mutational signatures are found in a variety of different types of cancer
Rogozin, I. B., Goncearenco, A., Lada, A. G., De, S., Yurchenko, V., Nudelman, G., Panchenko, A. R., Cooper, D. N., & Pavlov, Y. I. (2018) · Cell Cycle · doi:10.1080/15384101.2017.1404208 · Cited by 39 · see citing works
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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.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-12-07
- Volume
- 6
- Issue
- 1
- Pages
- 38133-38133
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5141443
- 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
- gold
- doi.org
- 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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