Gene expression in cancer is regulated by genomic aberrations, such as gene mutations and copy number abnormalities, as well as epigenomic aberrations, such as DNA methylation, histone modifications, and chromatin conformation changes. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignant epithelial tumor; however, its epigenomic aberrations have not been completely elucidated. We conducted comprehensive analyses of epigenomes in NPC by circular chromosome conformation capture sequencing (4C-seq), high-throughput chromosome conformation capture sequencing (Hi-C), chromatin immunoprecipitation sequencing (ChIP-seq), and ribonucleic acid sequencing (RNA-seq). In the genome of EBV (+) NPC cells (C666-1), 50 regions were present, where the EBV genome interacted (EBV-interacting regions, EBVIRs); they were significantly AT-rich and gene-poor compared with other regions. Hi-C analysis revealed that more than 90% of EBVIRs were repressed compartments in normal epithelial cells (NP69T), which suggested that they were heterochromatin regions. ChIP-seq showed low signals of active histone marks, including H3K27ac and H3K4me1, in NP69T cells; however, these increased in C666-1 cells, indicating aberrant activation of enhancers that promote gene expression. Within the EBVIR-overlapping topologically associating domains, 14 H3K4me3(+) genes were significantly upregulated in C666-1 cells. One of the target genes, PLA2G4A, interacted with enhancers activated in EBVIRs and was highly expressed in NPC; its knockdown significantly reduced cell proliferation. These results suggest that the EBV genome contributes to the carcinogenesis of NPC by activating enhancers within the suppressed heterochromatin in host cells.

Introduction: Tonsillectomy is useful for reducing fever attacks in patients with PFAPA syndrome. However, this disease may improve naturally with growth. Therefore, the optimal timing for surgery remains unclear.

Methods: We compared the long-term prognosis of 41 children with PFAPA syndrome, with 18 and 23 patients in the surgical and non-surgical groups, respectively. Prognosis factors, such as sex, tonsil hypertrophy, adenoid proliferation, and onset time, were investigated.

Results: The disease duration shortened by 3 years and 7 months in the surgical group compared to the non-surgical group. In children in whom the onset time was ≥2 years, the disease duration shortened to 4 years and 5 months compared to the non-surgical group.

Discussion: Age at onset of ≥2 years can be a criterion for determining whether surgery is appropriate. Several studies have reported differences in histology and microbiota features compared with normal tonsils. Further consideration of studies using onset age as an evaluation axis may elucidate triggering factors and pathogenesis.