Integrative Multi-Omics Studies for Precision Oncology in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma (NPC) - by Dr. Wei Dai

 

Abstract:

NPC has a distinct geographical distribution, endemic in Southeast Asia but rare worldwide. Epstein-Barr virus (EBV) is detected in over 90% of NPC cases in the endemic regions such as Hong Kong. Genome-wide association studies and epidemiology analyses suggest that genetic predisposition, environmental factors, and EBV high-risk subtypes are strong risk factors for NPC. To understand the molecular basis of NPC, we utilized the multi-omics approaches including whole-genome bisulfite sequencing (WGBS), assay for transposase-accessible chromatin using sequencing (ATAC-Seq), whole-exome sequencing (WES), bulk RNA sequencing and single-cell RNA sequencing (scRNA-Seq) data to characterize the molecular subtypes in EBV+ NPC. The genetic and epigenetic heterogeneity in EBV+ NPC was discovered by these multi-omics approaches. The results show that the APOBEC family plays an important role in orchestrating the genomic and epigenomic landscape in NPC. Moreover, we provide evidence that EBV infection is associated with reprogramming of the 2D regulatory epigenome and 3D genome architecture, leading to the EBV-specific cell communications between cancer and immune cells in the immune suppressive tumor microenvironment (TME). These findings link host factors, EBV-associated epigenetic dysregulation, TME, and immune evasion together, and highlight the importance of molecular subtyping for precision oncology in EBV+ NPC.