Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer:...

Area of Science:

• Oncology
• Virology
• Genomics

Background:

• The precise causes of breast cancer remain largely unknown.
• Epstein-Barr virus (EBV), a widespread lifelong infection, is a potential risk factor for breast cancer.
• EBV-infected mammary cells promote breast cancer in animal models, suggesting a link between viral infection and malignancy.

Purpose of the Study:

• To investigate the hypothesis that EBV infection contributes to breast cancer development by causing lasting genomic damage.
• To determine if EBV-induced genomic alterations compromise the body's natural safeguards against cancer.

Main Methods:

• Comparative analysis of publicly available genome data from approximately 2100 breast cancers and 25 ovarian cancers.
• Comparison with genome data from EBV-associated cancers, including nasopharyngeal cancer, lymphomas, and gastric cancer.
• Development of specialized algorithms for accurate comparison of chromosome breakpoints and genomic variations.

Main Results:

• Chromosome breakpoints in breast and ovarian cancers significantly clustered around those found in EBV-associated cancers.
• Viral breakpoint clusters were identified across various breast cancer subtypes, disrupting genes crucial for cancer protection.
• Evidence of integrated EBV genome fragments and compromised host defenses (piRNA, MHC) found in breast cancers, indicating permanent viral damage.

Conclusions:

• EBV infection is a predisposing factor for breast cancer and metastasis, with effects persisting even after viral clearance.
• Identification of EBV-driven pathogenic genomic damage offers potential for improved cancer screening, treatment, and prevention.
• Childhood immunization against EBV may offer protection against various cancers and potentially other chronic diseases.