APOBEC-mediated DNA alterations: A possible new mechanism of carcinogenesis in EBV-positive gastric cancer
| Autor: | Rodrigo Duarte Drummond, Israel Tojal da Silva, Helano C. Freitas, Joao Lima, Irina Bobrovnitchaia, Maria João Amorim, Diana N. Nunes, Renan Valieris, Thais Fernanda Bartelli, Emmanuel Dias-Neto |
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| Rok vydání: | 2018 |
| Předmět: |
APOBEC
Cancer Research Herpesvirus 4 Human Genes Viral Somatic cell Carcinogenesis Biology medicine.disease_cause Transcriptome 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Stomach Neoplasms Cytidine Deaminase medicine Humans APOBEC Deaminases Mutation Cancer DNA Neoplasm medicine.disease Oncology chemistry 030220 oncology & carcinogenesis Cancer research DNA |
| Zdroj: | International journal of cancerReferences. 146(1) |
| ISSN: | 1097-0215 |
| Popis: | Mechanisms of viral oncogenesis are diverse and include the off-target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single-strand DNA editing capability of APOBECs represent a well-conserved viral infection response that can also cause untoward mutations in host DNA. Here we show, after evaluating somatic single-nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA-expression and the APOBEC-mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC-mutations preferentially occuring in transcriptionally-active loci. The EBV-infection and APOBEC3 mutation-signature axis was confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV-induced gastric carcinogenesis. After further validation, this EBV-APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted. |
| Databáze: | OpenAIRE |
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