{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:13:42Z","timestamp":1791087222446,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients treated with <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> inhibitors (e.g. vemurafenib), a novel targeted therapy for advanced melanoma harbouring certain <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> mutations, develop numerous adverse cutaneous side effects, including skin tumors such as squamous cell carcinoma or non\u2010malignant verruciform keratinocyte proliferations, termed \u2018<jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>\u2010inhibitor\u2010associated verrucous keratosis (<jats:styled-content style=\"fixed-case\">BAVK<\/jats:styled-content>) lesions\u2019. These keratinocyte proliferations are believed to be caused by paradoxical hyperactivation of the <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathway in cells with wild\u2010type <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>, but mutated <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>. However, due to the clinical and histological verruca\u2010like appearance of these lesions, additional aetiologic cofactors, such as infectious agents (i.e. oncogenic viruses), might be suspected. Therefore, we performed 454 high\u2010throughput sequencing of <jats:styled-content style=\"fixed-case\">BAVK<\/jats:styled-content> lesions from vemurafenib\u2010treated patients on the transcript level to identify actively transcribed viral sequences of known [e.g. human papilloma viruses (<jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>)] or even yet\u2010unknown viruses. Next\u2010generation sequencing did not identify transcripts of any human viruses out of 1\u00a0595\u00a0161 reads obtained from <jats:styled-content style=\"fixed-case\">BAVK<\/jats:styled-content> lesions of four patients. Nevertheless, all controls were recognized correctly, and the detection of sequences derived from the cutaneous microbiome (e.g. skin commensals and bacterial phages) confirmed the validity and sensitivity of the sequencing data. Our results are consistent with preliminary histological and immunohistochemical findings recently reported by others, who also failed to detect the expression of <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> proteins in <jats:styled-content style=\"fixed-case\">BAVK<\/jats:styled-content>. Although the patient number is limited and we cannot exclude the possibility of having missed a viral transcript of very low abundance, our study argues against a viral aetiology of <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>\u2010inhibitor\u2010associated verruciform keratoses occurring under vemurafenib.<\/jats:p>","DOI":"10.1111\/exd.12249","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T22:00:46Z","timestamp":1381528846000},"page":"725-729","source":"Crossref","is-referenced-by-count":22,"title":["No human virus sequences detected by next\u2010generation sequencing in benign verrucous skin tumors occurring in <scp>BRAF<\/scp>\u2010inhibitor\u2010treated patients"],"prefix":"10.1111","volume":"22","author":[{"given":"Tina","family":"Ganzenmueller","sequence":"first","affiliation":[{"name":"Institute of Virology Hannover Medical School Hannover 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