Topic
APOBEC
About: APOBEC is a research topic. Over the lifetime, 486 publications have been published within this topic receiving 34400 citations. The topic is also known as: APOBEC Deaminase & APOBEC Deaminases.
Papers published on a yearly basis
Papers
Wellcome Trust Sanger Institute1, Wellcome Trust2, Cambridge University Hospitals NHS Foundation Trust3, University of British Columbia4, University of Cambridge5, Oslo University Hospital6, The Breast Cancer Research Foundation7, University of Oslo8, University of Münster9, Université libre de Bruxelles10, German Cancer Research Center11, University of Iceland12, Erasmus University Rotterdam13, Paris Descartes University14, French Institute of Health and Medical Research15, University of Paris16, Broad Institute17, University of Bergen18, University of Queensland19, University of Oviedo20, University of Glasgow21, Harvard University22, United States Department of Veterans Affairs23, Netherlands Cancer Institute24, University of Kiel25, Radboud University Nijmegen26, King's College London27, Curie Institute28, Bankstown Lidcombe Hospital29, University of New South Wales30, University of Barcelona31
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Abstract: All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
9,666 citations
Wellcome Trust Sanger Institute1, Flanders Institute for Biotechnology2, Katholieke Universiteit Leuven3, Norwich Research Park4, University of East Anglia5, Lund University6, Harvard University7, Oslo University Hospital8, King's College London9, Erasmus University Rotterdam10, University of British Columbia11, Curie Institute12, The Breast Cancer Research Foundation13, Medical Research Council14, University of Cambridge15, Cambridge University Hospitals NHS Foundation Trust16
TL;DR: This work generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes, finding a remarkable phenomenon of localized hypermutation, termed “kataegis,” was observed.
2,002 citations
TL;DR: It is demonstrated that APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-Ahypermutation in the nascent retroviral DNA, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.
Abstract: Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes When produced in the presence of APOBEC3G, vif-defective virus is non-infectious APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA APOBEC family members also have potent DNA mutator activity through dC deamination; however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens
1,598 citations
TL;DR: It is shown that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates withAPOBEC mRNA levels, and that ubiquitous APOBec-mediated Mutagenesis are carcinogenic.
Abstract: Recent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels. Mutation clusters in whole-genome and exome data sets conformed to the stringent criteria indicative of an APOBEC mutation pattern. Applying these criteria to 954,247 mutations in 2,680 exomes from 14 cancer types, mostly from The Cancer Genome Atlas (TCGA), showed a significant presence of the APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers, reaching 68% of all mutations in some samples. Within breast cancer, the HER2-enriched subtype was clearly enriched for tumors with the APOBEC mutation pattern, suggesting that this type of mutagenesis is functionally linked with cancer development. The APOBEC mutation pattern also extended to cancer-associated genes, implying that ubiquitous APOBEC-mediated mutagenesis is carcinogenic.
1,187 citations
TL;DR: 25 spatially distinct regions from seven operable NSCLCs were sequenced and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification, and pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity.
Abstract: Spatial and temporal dissection of the genomic changes occurring during the evolution of human non–small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.
1,116 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 16 |
| 2024 | 45 |
| 2023 | 142 |
| 2022 | 90 |
| 2021 | 53 |
| 2020 | 53 |