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Viral Load, Integra...
Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas
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- Lillsunde-Larsson, Gabriella, 1971- (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Region Örebro län,Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden
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- Helenius, Gisela, 1973- (författare)
- Örebro universitet,Institutionen för läkarutbildning,Region Örebro län,Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden
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- Sorbe, Bengt, 1947- (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Region Örebro län,Department of Oncology, Örebro University Hospital, Örebro, Sweden
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- Karlsson, Mats G., 1960- (författare)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Region Örebro län,Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden
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(creator_code:org_t)
- 2014-11-13
- 2014
- Engelska.
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 9:11
- Relaterad länk:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.Results: Vaginal tumors were found to have a higher viral load (p=0.024) compared to vulvar tumors but a high copy number (> median value, 15 000) as well as high methylation (> 50%) was significantly (p=0.010 and p=0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150 000 copies not highly methylated (n=25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n=6, 11.1%); (3) tumors with viral DNA fully integrated (n=11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium-or unmethylated (< 50%) and having a high viral load (> total mean value 150 000; n=12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.Conclusion: HPV16-related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-related parameters were found to be of clinical importance in the vulvar series only.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (ämneskategori)
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