Breakpoints on chromosome 8 in breast cancer genomes cluster around breakpoints in EBV-associated cancer genomes.

Epstein-Barr virus (EBV) infection of mammary cells produces breast tumors in immunosuppressed mice and breast tissues from patients are about five times more likely to be EBV-positive than tissues from healthy controls. However, infection data are conflicting so a role for EBV in breast cancer is not broadly accepted. Malignant cells can lose EBV infection, but the virus may have left behind characteristic damage that caused the malignancy. Bioinformatic methods were developed to identify persistent viral damage in breast cancer genomes even if EBV infection has disappeared. Breast cancer cells exhibited residual epigenetic scars resembling cells with a cleared EBV infection. Epigenetic changes affecting breast cancer driver genes clustered around epigenetic changes in EBV-related cancers. Gene defects in hereditary breast cancers approximated tumor suppressive mechanisms deleted in EBV-associated cancers. Metabolic reprogramming in breast cancer was traced to EBV-related deletions. Focal amplifications and somatic hypermutation that drive breast cancer clustered around breakpoints in EBV-mediated cancers. These breakpoints may be due to EBV nucleases released by the lytic switch or to deregulated estrogen receptor-mediated responses. Alternate explanations were ruled out. The human genome contains fragments of an EBV oncogenic protein, but a childhood anti-EBV vaccine is still feasible to protect against breast cancer. Persistent damage from even a cleared viral infection emphasizes the health benefits of vaccinations.