| Autor: |
M. C. Siciliano, S. Tornambè, G. Cevenini, E. Sorrentino, M. Granai, G. Giovannoni, D. Marrelli, I. Biviano, F. Roviello, H. Yoshiyama, L. Leoncini, S. Lazzi, L. Mundo |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Infectious Agents and Cancer, Vol 17, Iss 1, Pp 1-12 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1750-9378 |
| DOI: |
10.1186/s13027-022-00469-5 |
| Popis: |
Abstract Background The Epstein-Barr virus (EBV) causes various B-cell lymphomas and epithelial malignancies, including gastric cancer (GC) at frequencies ranging from 5 to 10% in adenocarcinomas (ADK) to 80% in GC with lymphoid stroma (GCLS). Using high-sensitivity methods, we recently detected EBV traces in a large cohort of EBV-negative B-cell lymphomas, suggesting a hit-and-run mechanism. Methods Here, we used routine and higher-sensitivity methods [droplet digital PCR (ddPCR) for EBV segments on microdissected tumour cells and RNAscope for EBNA1 mRNA] to assess EBV infection in a cohort of 40 GCs (28 ADK and 12 GCLS). Results ddPCR documented the presence of EBV nucleic acids in rare tumour cells of several cases conventionally classified as EBV-negative (ADK, 8/26; GCLS, 6/7). Similarly, RNAscope confirmed EBNA1 expression in rare tumour cells (ADK, 4/26; GCLS, 3/7). Finally, since EBV induces epigenetic changes that are heritable and retained after complete loss of the virus from the host cell, we studied the methylation pattern of EBV-specifically methylated genes (Timp2, Eya1) as a mark of previous EBV infection. Cases with EBV traces showed a considerable level of methylation in Timp2 and Eya1 genes that was similar to that observed in EBER-ISH positive cases and greater than cases not featuring any EBV traces. Conclusions These findings suggest that: (a) EBV may contribute to gastric pathogenesis more widely than currently acknowledged and (b) indicate the methylation changes as a mechanistic framework for how EBV can act in a hit-and-run manner. Finally, we found that the viral state was of prognostic significance in univariate and multivariate analyses. |
| Databáze: |
Directory of Open Access Journals |
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