Polyomavirus large T antigen is prevalent in urothelial carcinoma post–kidney transplant

Yan, Ling; Salama, Mohamed E.; Lanciault, Christian; Matsumura, Linh; Troxell, Megan L.

doi:10.1016/j.humpath.2015.09.021

Cited by 33 publications

(26 citation statements)

References 36 publications

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“…There is growing evidence that reactivation of polyomavirus infection under immunosuppression might play an important role in the development of aggressive UC after renal transplantation . A driving role of BKPyV infection is also supported by the low mutational load in cancer‐related genes in our case as compared with common UCs, which show some of the highest mutation rates among malignant human tumours .…”

Section: Resultssupporting

confidence: 56%

Donor‐derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus

Müller

Rämö

Naegele

et al. 2018

The Journal of Pathology

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BK polyomavirus has been linked to urothelial carcinoma in immunosuppressed patients. Here, we performed comprehensive genomic analysis of a BK polyomavirus-associated, metachronous, multifocal and metastatic micropapillary urothelial cancer in a kidney transplant recipient. Dissecting cancer heterogeneity by sorting technologies prior to array-comparative genomic hybridization followed by short tandem repeat analysis revealed that the metastatic urothelial cancer was of donor origin (4-year-old male). The top 50 cancer-associated genes showed no key driver mutations as assessed by next-generation sequencing. Whole genome sequencing and BK polyomavirus-specific amplification provided evidence for episomal and subgenomic chromosomally integrated BK polyomavirus genomes, which carried the same unique 17-bp deletion signature in the viral non-coding control region (NCCR). Whereas no role in oncogenesis could be attributed to the host gene integration in chromosome 1, the 17-bp deletion in the NCCR increased early viral gene expression, but decreased viral replication capacity. Consequently, urothelial cells were exposed to high levels of the transforming BK polyomavirus early proteins large tumour antigen and small tumour antigen from episomal and integrated gene expression. Surgery combined with discontinuation of immunosuppression resulted in complete remission, but sacrificed the renal transplant. Thus, this report links, for the first time, BK polyomavirus NCCR rearrangements with oncogenic transformation in urothelial cancer in immunosuppressed patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Resultssupporting

confidence: 56%

Donor‐derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus

Müller

Rämö

Naegele

et al. 2018

The Journal of Pathology

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“…First, we assessed the integration of oncogenic viruses, which is identified in various tumours with a high incidence in immunosuppressed patients, such as HPV in vaginal cancer, EBV in iatrogenic immunodeficiency‐associated lymphoproliferative disorders, and HHV‐8 in Kaposi sarcoma. Recently, the integration of the BK virus (BKV) was shown in urothelial carcinoma in post‐renal transplant patients . We therefore evaluated its status in uterine ATs.…”

Section: Discussionmentioning

confidence: 99%

Adenomatoid tumour of the uterus is frequently associated with iatrogenic immunosuppression

et al. 2018

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“…Recent years have seen increased published experience in case reports and small series of high grade, mostly urothelial carcinomas arising at different locations in the urinary tract in the setting of immunosuppression, usually post‐transplant, and expressing the polyoma virus T‐antigen of the BK virus . These carcinomas have included, however, tumors classified morphologically as collecting duct carcinoma, including two cases reported within the classic large series of CDC and RMC reported by Gupta et al .…”

Section: Differential Diagnoses and Emerging Entitiesmentioning

confidence: 99%

High grade infiltrative adenocarcinomas of renal cell origin: New insights into classification, morphology, and molecular pathogenesis

Singh

Ohe

Smith

2018

Pathology International

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Collecting duct carcinoma was described over 30 years ago as a renal tumor, based in the medullary collecting system, with tubulopapillary morphology, prominent infiltrative growth, and stromal desmoplasia. While diagnostic workup has always emphasized exclusion of upper tract urothelial carcinoma and metastatic adenocarcinoma to the kidney, the molecular era of renal cell carcinoma classification has enabled recognition of and provided tools for diagnosis of new entities in this morphologic differential. In this review, we consider these developments, with emphasis on renal medullary carcinoma, closely related renal cell carcinoma, unclassified with medullary phenotype, and fumarate hydratase-deficient renal cell carcinoma. Integration of ancillary studies with suggestive patterns of morphology is emphasized for practical implementation in contemporary diagnosis, and several emerging tumor types in the morphologic differential are presented.

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Polyomavirus large T antigen is prevalent in urothelial carcinoma post–kidney transplant

Cited by 33 publications

References 36 publications

Donor‐derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus

Donor‐derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus

Adenomatoid tumour of the uterus is frequently associated with iatrogenic immunosuppression

High grade infiltrative adenocarcinomas of renal cell origin: New insights into classification, morphology, and molecular pathogenesis

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