title: BK Polyomavirus Infection and Renourinary Tumorigenesis.
abstract: BK polyomavirus (BKPyV) infection represents a major problem in transplantation, particularly for renal recipients developing polyomavirus-associated nephropathy (PyVAN). The possibility that BKPyV may also be oncogenic is not routinely considered. Twenty high-grade renourinary tumors expressing polyomavirus large T antigen in the entirety of the neoplasm in 19 cases, including the metastases in six, have been reported in transplant recipients with a history of PyVAN or evidence of BKPyV infection. Morphological and phenotypical features consistent with inactivation of the tumor suppressors pRB and p53 were found in the bladder tumors, suggesting a carcinogenesis mechanism involving the BKPyV large tumor oncoprotein/antigen. The pathogenesis of these tumors is unclear, but given the generally long interval between transplantation and tumor development, the risk for neoplasms after BKPyV infections may well be multifactorial. Other elements potentially implicated include exposure to additional exogenous carcinogens, further viral mutations, and cell genomic instability secondary to viral integration, as occurs with the Merkel cell PyV-associated carcinoma. The still scarce but increasingly reported association between longstanding PyVAN and renourinary neoplasms requires a concerted effort from the transplant community to better understand, diagnose, and treat the putative association between the BKPyV and these neoplasms.
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: J C
authors.initials: JC
authors.lastname: Papadimitriou
authors.affiliation: Division of Transplantation Pathology, Department of Pathology, The Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania, PA.
authors.forename: P
authors.initials: P
authors.lastname: Randhawa
authors.affiliation: Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
authors.forename: C Hanssen
authors.initials: CH
authors.lastname: Rinaldo
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: C B
authors.initials: CB
authors.lastname: Drachenberg
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: B
authors.initials: B
authors.lastname: Alexiev
authors.affiliation: Metabolic and Renal Research Group, UiT, The Arctic University of Norway, Tromsø, Norway.|Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.|Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: H H
authors.initials: HH
authors.lastname: Hirsch
mesh_terms: D001739:BK Virus / Q000472:pathogenicity*; D063646:Carcinogenesis / Q000473:pathology*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D027601:Polyomavirus Infections / Q000150:complications* / Q000821:virology; D011379:Prognosis; D014412:Tumor Virus Infections / Q000150:complications* / Q000821:virology; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000473:pathology
keywords: cancer; cancer malignancy neoplasia; clinical research practice; histopathology; infection and infectious agents, viral, infection and infectious agents, viral: BK / JC / polyoma; infectious disease; kidney transplantation; malignancy neoplasia risk factors; nephrology pathology