title: Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers.
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.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.|Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Rogozin
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.|Department Microbiology and Molecular Genetics, University of California, Davis, CA, USA.
authors.forename: Artem G
authors.initials: AG
authors.lastname: Lada
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Goncearenco
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.affiliation: Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Subhajyoti
authors.initials: S
authors.lastname: De
authors.affiliation: Department of Neurology and Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: German
authors.initials: G
authors.lastname: Nudelman
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Panchenko
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.|Departments of Microbiology and Pathology, Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Youri I
authors.initials: YI
authors.lastname: Pavlov
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics*; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009700:Nucleoside Deaminases / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics
chemical_list: D009711:Nucleotides; D003596:Cytosine; D009700:Nucleoside Deaminases