Comparative genomic landscape of patients with lung cancer with high-load versus low-load Epstein-Barr virus infection.

e20017 Background: As the first known oncogenic virus, Epstein–Barr virus (EBV) has been proven to be associated with nasopharyngeal carcinoma, gastric cancer, and lymphomas. Its relationship with lung cancer, however, remains ambiguous. Given that over 90% of adults globally harbor EBV infections and that EBV can be detected in the tumor cells of lung cancer patients, we hypothesize that lung cancer may be associated with high-load EBV infection, whereas low-load infection is less likely. Here, we compared the genomic landscapes of lung cancer patients with high-load and low-load EBV infections. Methods: We conducted a study on 2, 268 Chinese lung cancer patients, collecting tumor tissue samples for analysis. Targeted sequencing of 680 cancer-related genes and EBV genome was performed using the HapOnco StarPanel NGS Assay (HaploX Biotechnology, Shenzhen). The EBV infection load was evaluated based on the proportion of reads aligned to the EBV reference genome in the total sequenced reads for each patient. 99% of these samples could be detected with at least two EBV reads. From them, we selected a total of 32 high-load EBV cases (2. 1% - 64. 3%) and 35 low-load EBV cases (0. 1% - 1. 7%). Their genomic profiles and altered signaling pathways were subsequently analyzed. Results: In the high-load EBV group, we identified 122 somatic mutations with no recurrent mutations between cases. As for genes, the most frequently mutated were TP53 (25. 0%), LRP1B (15. 6%), NFKBIA (12. 5%), ERBB4 (9. 4%), and CNTNAP5 (9. 4%), with these mutations being notably enriched in EBV infection pathways according to KEGG, and IL−7 Signal Transduction pathways as per BioCarta. The most common copy number variation events were FGFR3 (12. 5%), CDKN2A (12. 5%) and FOXP1 (12. 5%) gene deletions. In contrast, the low-load EBV group presented with 316 somatic mutations, with the most recurrent mutations being EGFR L858R (17. 1%) and E746A750del (17. 1%). The top frequently mutated genes were TP53 (55. 3%), EGFR (44. 7%), ARID1A (10. 5%) and KRAS (10. 5%). Conclusions: The genomic profiles of lung cancer patients with high-load EBV infection differ significantly from those with low-load infection. Notably, the genomic mutations in the high-load EBV group are closely associated with EBV infection, suggesting that high-load EBV infection may be linked to lung cancer, unlike low-load infection.