Epstein-Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin.

作者: Octavia Ramayanti , Hedy Juwana , Sandra A.M.W. Verkuijlen , Marlinda Adham , Michiel D. Pegtel

DOI: 10.1002/IJC.30418

关键词:

摘要: Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr virus (EBV) as oncogenic driver. NPC often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load RNA transcripts in (NP) brushings useful for minimally invasive diagnosis. However, whether these markers relate local replication or reflect tumor origin remains be demonstrated. To resolve this, we analysed EBV-DNA characteristics quantified latent lytic viral NP matching frozen NP-biopsy specimens from patients suspected having NPC. We observed non-fragmented Cp-promotor methylated both biopsies suggestive origin. Using quantitative RT-PCR determined expression levels 7 critical (EBER1, Qp-EBNA1, EBNA2, BART, LMP1, LMP2, BARF1) 5 (Zta, Rta, TK, PK VCA-p18) transcripts. Although early were frequently detected conjunction high load, the prevailed reflected a typical NPC-associated latency-II transcription profile without EBNA2. Late rare at low mainly brushings, abortive reactivation rather than complete replication. EBV-IgA serology (EBNA1, VCA, Zta) did not correlate level situ. Overall, profiling, fragmentation methylation analysis parallel indicate brush sampling provides true robust indicator presence.

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