{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:03:11Z","timestamp":1790820191855,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer society","doi-asserted-by":"crossref","award":["KWF VU2011-4809"],"award-info":[{"award-number":["KWF VU2011-4809"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein\u2010Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load and RNA transcripts in nasopharyngeal (NP) brushings is useful for minimally invasive NPC diagnosis. However, whether these EBV markers relate to local virus replication or reflect tumor origin remains to be demonstrated. To resolve this, we analysed EBV\u2010DNA characteristics and quantified latent and lytic viral RNA transcripts in NP brushings and matching frozen NP\u2010biopsy specimens from patients suspected of having NPC.<\/jats:p>\n                  <jats:p>We observed non\u2010fragmented and Cp\u2010promotor methylated EBV\u2010DNA in both NP brushings and biopsies suggestive of tumor origin. Using quantitative RT\u2010PCR we determined expression levels of 7 critical latent (EBER1, Qp\u2010EBNA1, EBNA2, BART, LMP1, LMP2, BARF1) and 5 lytic (Zta, Rta, TK, PK and VCA\u2010p18) RNA transcripts. Although latent and early lytic RNA transcripts were frequently detected in conjunction with high EBV viral load, in both brushings and biopsies the latent transcripts prevailed and reflected a typical NPC\u2010associated latency\u2010II transcription profile without EBNA2. Late lytic RNA transcripts were rare and detected at low levels mainly in NP brushings, suggestive of abortive viral reactivation rather than complete virus replication. EBV\u2010IgA serology (EBNA1, VCA, Zta) did not correlate to the level of viral reactivation in situ.<\/jats:p>\n                  <jats:p>Overall, viral RNA profiling, DNA fragmentation and methylation analysis in NP brushings and parallel biopsies indicate that NP brush sampling provides a true and robust indicator of NPC tumor presence.<\/jats:p>","DOI":"10.1002\/ijc.30418","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T06:09:38Z","timestamp":1473228578000},"page":"149-162","source":"Crossref","is-referenced-by-count":59,"title":["Epstein\u2010Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin"],"prefix":"10.1002","volume":"140","author":[{"given":"Octavia","family":"Ramayanti","sequence":"first","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The 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