Abstract 3178: Metastatic urothelial cancer 10 years after transplanting a filial kidney: genomically investigating the perpetrator
Authors: David C. Müller, Maarit Raemoe, Christian Wetterauer, Valeria Perrina, Luca Quagliata, Tatjana Vlajnic, Christian Ruiz, Beate Balitzki, Hans H. Hirsch, Rainer Grobholz, Lukas Bubendorf, Cyrill A. Rentsch
Journal: Cancer Research (2016)

Abstract BACKGROUND Polyomavirus (BKV) infection has been associated with development of urothelial carcinoma (UC). We report on a patient with conventional UC of the bladder (Ta, G3) 8 years after receiving a kidney graft from a 4 year old male donor. After a recurrence (T1, G3) 9 years after transplantation (NTx), he was diagnosed with a SV-40 positive metastatic micropapillary and muscle-invasive UC 10 years after NTx with involvement of the graft kidney pelvis (pT3), the bladder (pT3) and a pelvic lymphnode metastasis. The aim of this study was to investigate the genealogy and clonal relationship between these cancer locations. METHODS Cancer cell nuclei derived from formalin fixed tumor specimens were processed and sorted based on DNA content with a BD Influx FACS. DNA from sorted aneuploid populations was analyzed by whole genome high resolution CGH microarrays (aCGH). In addition, short tandem repeat (STR) analyses were done with the PowerPlex® ESI Kit commercial testing kit. Each run was performed on an Applied Biosystems Genetic Analyzer 3500 and analyzed with the GeneMapper ID-X Software. Integration of PV-genom was investigated by RT-PCR. The IonTorrent platform by LifeTech (PGM, IonAmpliseq Cancer Hotspot Panel v2) was used for next-generation-sequencing (NGS). RESULTS Array CGH clarified that the primary two non-muscle invasive bladder tumors differed completely from each other and from the subsequent cancer tissues. The tumor manifestations 10 years after NTx shared the same genomic profile, except for a private amplification at 6p12.3 and a private deletion at Xp22.33 - Xp22.11, both in the bladder tumor. STR identified all three tumors diagnosed 10 years after NTx to originate from the allograft donor. NGS identified two shared mutations of unknown relevance (KDR / InDel chr4:55962545; Akt1 / c.138C&amp;gt;A) in the 10 year after NTx UC sites. No known somatic mutation was found. RT-PCR identified the PV to be integrated in the human cancer genome. Further studies are currently ongoing to define the exact integration sites of BKV and the potentially influenced human genes. CONCLUSIONS This case is an impressive example of a, donor-derived, metastatic micropapillary UC developed under immuno-suppression and subsequent BKV-reactivation in a presumably healthy transplanted kidney of a four years old donor. Citation Format: David C. Müller, Maarit Raemoe, Christian Wetterauer, Valeria Perrina, Luca Quagliata, Tatjana Vlajnic, Christian Ruiz, Beate Balitzki, Hans H. Hirsch, Rainer Grobholz, Lukas Bubendorf, Cyrill A. Rentsch. Metastatic urothelial cancer 10 years after transplanting a filial kidney: genomically investigating the perpetrator. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3178.