Drummond, Rodrigo D.
Lima, Joao P.
Freitas, Helano C.
Bartelli, Thais F.
de Amorim, Maria G.
Nunes, Diana N.
da Silva, Israel T.
Total Authors: 10
 AC Camargo Canc Ctr, Lab Bioinformat & Computat Biol, BR-01509010 Sao Paulo, SP - Brazil
 AC Camargo Canc Ctr, Med Oncol Dept, Sao Paulo, SP - Brazil
 AC Camargo Canc Ctr, Lab Med Genom, BR-01509010 Sao Paulo, SP - Brazil
 Univ Sao Paulo, Fac Med, Inst Psychiat, Lab Neurosci, Sao Paulo, SP - Brazil
Total Affiliations: 4
International Journal of Cancer;
JAN 1 2020.
Web of Science Citations:
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)