In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.

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.

Allele frequencies and forensically relevant population statistics of 16 STR loci, including the new European Standard Set (ESS) loci, were estimated from 668 unrelated individuals of Caucasian appearance living in different parts of Switzerland. The samples were amplified with a combination of the following three kits: AmpFlSTR® NGM SElect™, PowerPlex® ESI17 and PowerPlex® ESX 17. All loci were highly polymorphic and no significant departure from Hardy-Weinberg equilibrium and linkage equilibrium was detected after correction for sampling.

In forensic examination it is a standard to take vaginal swabs from victims of sexual assault for further molecular genetic analysis. Laboratories then are usually confronted with mixtures of lots of female and only a small amount of male DNA. Nowadays it is possible to work with specific Y chromosomal markers after DNA extraction by differential lysis. The determined ratio of autosomal DNA and Y chromosomal DNA can be used to identify the possibility of generating a male profile in these samples.

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>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.