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Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients

التفاصيل البيبلوغرافية
العنوان: Evidence for virus-mediated oncogenesis in bladder cancers arising in solid organ transplant recipients
المؤلفون: Gabriel J Starrett, Kelly Yu, Yelena Golubeva, Petra Lenz, Mary L Piaskowski, David Petersen, Michael Dean, Ajay Israni, Brenda Y Hernandez, Thomas C Tucker, Iona Cheng, Lou Gonsalves, Cyllene R Morris, Shehnaz K Hussain, Charles F Lynch, Reuben S Harris, Ludmila Prokunina-Olsson, Paul S Meltzer, Christopher B Buck, Eric A Engels
المصدر: eLife, Vol 12 (2023)
بيانات النشر: eLife Sciences Publications Ltd, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: polyomavirus, papillomavirus, bladder cancer, torque teno virus, solid organ transplant recipient, Medicine, Science, Biology (General), QH301-705.5
الوصف: A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/82690; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.82690
URL الوصول: https://doaj.org/article/276cdac8c65046efa937353d38e5f7ca
رقم الأكسشن: edsdoj.276cdac8c65046efa937353d38e5f7ca
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.82690