Details

Autor(en) / Beteiligte

• Ka-Yue Chow, Larry
• Lai-Shun Chung, Dittman
• Tao, Lihua
• Chan, Kui Fat
• Tung, Stewart Yuk
• Cheong Ngan, Roger Kai
• Ng, Wai Tong
• Wing-Mui Lee, Anne
• Yau, Chun Chung
• Lai-Wan Kwong, Dora
• Ho-Fun Lee, Victor
• Lam, Ka-On
• Liu, Jiayan
• Chen, Honglin
• Dai, Wei
• Lung, Maria Li

Titel

Epigenomic landscape study reveals molecular subtypes and EBV-associated regulatory epigenome reprogramming in nasopharyngeal carcinoma

Ist Teil von

• EBioMedicine, 2022-12, Vol.86, p.104357-104357, Article 104357

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Epstein-Barr virus (EBV) latent infection is associated with genome-wide epigenomic changes in several malignancies, but its role in epigenetic dysregulation remains unclear in nasopharyngeal carcinoma (NPC). To investigate EBV-associated epigenetic dysregulation, we performed a multi-omics study by integrating whole-genome bisulfite sequencing (WGBS), assay for transposase-accessible chromatin using sequencing (ATAC-Seq), whole-exome sequencing (WES), and single-cell RNA sequencing (scRNA-Seq) data. In addition to the known global DNA hypermethylated subtype, we discovered a novel subtype with global hypomethylation in EBV + NPC. The consistent EBV-specific differentially methylated regions (EBV-DMRs) in the human genome were identified from both subtypes and associated with loss of CTCF binding (P < 2.2e-16). Importantly, CTCF is a master chromatin regulator and CTCF protein was reduced in 45% of NPC cases, especially in those with advanced NPC (Stage IV vs. others: 62% vs. 38%, P = 0.034). This result links EBV with chromatin changes. The ATAC-Seq data suggest regulatory epigenome reprogramming through chromatin accessibility changes in EBV + NPC with altered CTCF binding and the switch of transcription factor binding from differentiation-associated KLF/SP family to the innate and adaptive immunity-related NF-ĸB and IRF families. Detailed chromatin accessibility analysis identified a potential EBV target gene CD74, which mediated EBV-specific cell-cell communications in the tumor microenvironment (TME) and was strongly correlated with T cell exhaustion (r2 = 0.55). Our study reveals the unexpected epigenetic heterogeneity, providing insights into NPC pathogenesis and highlighting the involvement of host factors in virus-associated epigenetic changes. EBV infection is associated with epigenome reprogramming and may promote immune evasion. This study was funded by the Hong Kong Research Grants Council grant (AoE/M-06/08) to MLL, General Research Fund (17103218 and 17102619) and seed funding for basic research (201611159158) to WD, and General Research Fund (17119618) to HC.