| Full text | |
| 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 Opportunities: | Research Projects - Thematic Grants |