APOBEC3A catalyzes mutation and drives carcinogenesis in vivo
| العنوان: | APOBEC3A catalyzes mutation and drives carcinogenesis in vivo |
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| المؤلفون: | Gabriel J. Starrett, Timothy K. Starr, Sandra Wagner, David A. Largaespada, Emily K. Law, Alexya N. Aguilera, Michael A. Carpenter, Michael B. Burns, Susan R. Ross, Hyoung Kim, Nuri A. Temiz, Lindsay K. Larson, Prokopios P. Argyris, Cameron Durfee, Rachel Isaksson Vogel, Rena Levin-Klein, Reuben S. Harris, Matthew C. Jarvis, Spyridon Stavrou |
| المصدر: | The Journal of Experimental Medicine |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, APOBEC, Infectious disease and host defense, Carcinogenesis, Hydrolases, Immunology, Mutagenesis (molecular biology technique), Loss of Heterozygosity, Mice, Transgenic, Biology, medicine.disease_cause, DNA sequencing, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Polyps, Cytidine Deaminase, Genome stability, Intestinal Neoplasms, medicine, Immunology and Allergy, Animals, Humans, RNA, Messenger, APOBEC3A, Solid Tumors, Genetics, Mutation, Base Sequence, Liver Neoplasms, Proteins, Liver Regeneration, 030104 developmental biology, chemistry, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, Biocatalysis, DNA Transposable Elements, Cytosine, DNA |
| الوصف: | The APOBEC mutation signature is abundant in cancer, but its relationship to the multistep process of carcinogenesis is unclear. Studies by Law and colleagues demonstrate that APOBEC3A catalyzes mutagenesis and promotes tumorigenesis in two different murine systems in vivo. The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis. All other APOBEC3 family members, including APOBEC3B, fail to promote liver tumor formation. Tumor DNA sequences from APOBEC3A-expressing animals display hallmark APOBEC signature mutations in TCA/T motifs. Bioinformatic comparisons of the observed APOBEC3A mutation signature in murine tumors, previously reported APOBEC3A and APOBEC3B mutation signatures in yeast, and reanalyzed APOBEC mutation signatures in human tumor datasets support cause-and-effect relationships for APOBEC3A-catalyzed deamination and mutagenesis in driving multiple human cancers. Graphical Abstract |
| تدمد: | 1540-9538 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9ba8178c2d5f053876081e771c5144c https://pubmed.ncbi.nlm.nih.gov/32870257 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c9ba8178c2d5f053876081e771c5144c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 |
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