RNA-based high-risk HPV genotyping and identification of high-risk HPV transcriptional activity in cervical tissues
| العنوان: | RNA-based high-risk HPV genotyping and identification of high-risk HPV transcriptional activity in cervical tissues |
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| المؤلفون: | Ruud L.M. Bekkers, Corina N. A. M. van den Heuvel, Johan Bulten, Albert G. Siebers, Diede L. Loopik, Karolina M. Andralojc, Duaa Elmelik, Martijn A. Huynen, Willem J. G. Melchers, Leon F.A.G. Massuger, William P.J. Leenders, Renée M.F. Ebisch |
| المصدر: | Modern Pathology, 33, 748-757 Modern Pathology, 33, 4, pp. 748-757 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cervical cancer, Transcriptional activity, Pathology, medicine.medical_specialty, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], RNA, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Biology, medicine.disease, Virology, Virus, Pathology and Forensic Medicine, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Transcription (biology), 030220 oncology & carcinogenesis, medicine, Cancer biomarkers, Line Probe Assay, Genotyping, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] |
| الوصف: | Contains fulltext : 218234.pdf (Publisher’s version ) (Closed access) Nearly all cervical cancers are initiated by a persistent infection with one of the high-risk human papillomaviruses (high-risk HPV). High-risk HPV DNA testing is highly sensitive but cannot distinguish between active, productive infections and dormant infections or merely deposited virus. A solution for this shortcoming may be the detection of transcriptional activity of viral oncogenes instead of mere presence of high-risk HPVs. In this study, fresh-frozen cervical tissues (n = 22) were subjected to high-risk HPV DNA detection using the line probe assay and to targeted RNA next-generation sequencing using single-molecule molecular inversion probes. Targeted RNA sequencing was applied for (1) RNA-based genotyping of high-risk HPV, giving information on specific HPV-subtype (2) discrimination of E2, E6, and E7 transcripts and (3) discovery of possible non-HPV cancer biomarkers. Data were analyzed using computational biology. Targeted RNA sequencing enabled reliable genotyping of high-risk HPV subtypes and allowed quantitative detection of E2, E6, and E7 viral gene expression, thereby discriminating cervical lesions from normal cervical tissues. Moreover, targeted RNA sequencing identified possible cervical cancer biomarkers other than high-risk HPV. Interestingly, targeted RNA sequencing also provided high-quality transcription profiles from cervical scrape samples, even after 1 week of dry storage or storage in Preservcyt fixative. This proof of concept study shows that targeted RNA sequencing can be used for high-risk HPV genotyping and simultaneous detection of high-risk HPV gene activity. Future studies are warranted to investigate the potential of targeted RNA sequencing for risk assessment for the development of cervical lesions, based on molecular analysis of cervical scrapes. |
| وصف الملف: | application/pdf |
| تدمد: | 0893-3952 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b6d72537b649d8362fa9b3c3483d349 http://hdl.handle.net/2066/218234 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1b6d72537b649d8362fa9b3c3483d349 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 08933952 |
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