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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

APOBEC-mediated DNA alterations: A possible new mechanism of carcinogenesis in EBV-positive gastric cancer

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Author(s):
Bobrovnitchaia, Irina [1] ; Valieris, Renan [1] ; Drummond, Rodrigo D. [1] ; Lima, Joao P. [1, 2] ; Freitas, Helano C. [3, 2] ; Bartelli, Thais F. [3] ; de Amorim, Maria G. [3] ; Nunes, Diana N. [3] ; Dias-Neto, Emmanuel [3, 4] ; da Silva, Israel T. [1]
Total Authors: 10
Affiliation:
[1] AC Camargo Canc Ctr, Lab Bioinformat & Computat Biol, BR-01509010 Sao Paulo, SP - Brazil
[2] AC Camargo Canc Ctr, Med Oncol Dept, Sao Paulo, SP - Brazil
[3] AC Camargo Canc Ctr, Lab Med Genom, BR-01509010 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Fac Med, Inst Psychiat, Lab Neurosci, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: International Journal of Cancer; v. 146, n. 1, p. 181-191, JAN 1 2020.
Web of Science Citations: 0
Abstract

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 the 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 occurring in the genomic loci of the most active transcripts. This EBV infection and APOBEC3 mutation-signature axis were 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. (AU)

FAPESP's process: 14/26897-0 - Epidemiology and genomics of gastric adenocarcinomas in Brazil
Grantee:Emmanuel Dias-Neto
Support type: Research Projects - Thematic Grants