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NPC268 whole-genome bisulfite sequencing (WGBS)

ABSTRACT: Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing (WGS) revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing (WGBS) and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively. Drug screening of NPC268 together with six other NPC cell lines using 339 compounds, representing the largest high-throughput drug testing in NPC, revealed biomarkers associated with specific drug classes. NPC268 represents the first and only available EBV-positive non-keratinizing differentiated NPC model, and extensive genomic, methylomic, transcriptomic, and drug response data should facilitate research in EBV and NPC, where current models are limited.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233426 | GEO | 2024/03/13

REPOSITORIES: GEO

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Project description:Nasopharyngeal carcinoma (NPC) is a challenging cancer that is rare in the United States but shows exceptionally high incidence in Southern China, Indonesia, and Malaysia. While the hallmark of NPC is striking geographic variation, early detection and clinical management are also critical characteristics of this cancer. The etiology of NPC is complex, involving the interplay of multiple factors, including Epstein Barr Virus (EBV), which appears to play an oncogenic role. While multimodality therapy is the mainstay of treatment for NPC, the impact of this treatment is greatly influenced by the presenting tumor stage, tumor size, nodal involvement, and the histologic subtype classification. Up to 40% percent of NPC cases present at an advanced stage, likely due to its deep location in the lymphatic-rich nasopharynx and its propensity for early lymphatic spread. Recent modifications in the TNM staging schema have attempted to improve prognostic accuracy, but variations in clinical outcome are still reported in patients with the same stage and similar treatment regimens. The various molecular markers developed to monitor disease progression have also proven unreliable. Hence, there is a significant need for a new kind of prognostic biomarker for NPC. Herein different approaches were applied to a set of samples to detect NPC-related miRNAs, potential circulating biomarkers. We have optimized the extraction of total RNA from NPC Formalin-fixed, paraffin-embedded (FFPE) samples and sera from four patients and matched controls and analyzed the miRNA expression profile by microarray, qPCR and RNAseq. The microarray analysis showed that 46 miRNAs were found to be differentially and significantly expressed in carcinogenic tissue compared to healthy tissue. Twenty-three (23) microRNAs were significantly upregulated (21 human microRNAs and 2 EBV miRNAs), whereas 13 were down-regulated. A total of 8 unique samples were analyzed on Agilent human miRNA microarray (miRBase Release 16.0). Of the 8 samples, 4 are from Non-keratinizing NPC tissue. Non-NPC (normal) tissue were taken from 4 individuals that were diagnosed with NPC (2 of which were matched/paired from the NPC case).

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NPC268 whole-genome bisulfite sequencing (WGBS)

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