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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.

SUBMITTER: Rogozin IB

PROVIDER: S-EPMC5141443 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Rogozin Igor B IB Lada Artem G AG Goncearenco Alexander A Green Michael R MR De Subhajyoti S Nudelman German G Panchenko Anna R AR Koonin Eugene V EV Pavlov Youri I YI

Scientific reports 20161207

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 ...[more]

PMID: 27924834

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