SUMMARY Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC) but there have been few whole genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these include highly recurrent tandem duplications involving an upstream enhancer of AR in 70-87% of cases compared with <2% of primary prostate cancers. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the noncoding mCRPC genome remain to be discovered.

No abstract

The paper focuses on intergenerational support relations between grandparents and their grandchildren in Germany, and how they have changed from 1996 to 2002. The paper begins with a brief review of the literature on functional aspects of the grandparent-grandchild relationship, after which the research hypotheses about intergenerational support in the relationship are elaborated. Following a description of the data source, the German Ageing Survey, and its samples and measures, the evidence on the patterns of grandparents' provision and receipt of intergenerational support to and from their grandchildren are presented and compared with parent-child support patterns. The analysis also considers variations by age groups and birth cohorts and changes over time. The main empirical finding is that there was a greater likelihood of financial transfers to grandchildren in 2002 than six years earlier. Nevertheless, the grandparents' relationships with their grandchildren remained imbalanced or asymmetrical, at the older generation's expense. It was found that financial and instrumental support patterns between grandparents and grandchildren were best explained using an 'intergenerational stake ' hypothesis rather than one of ' intergenerational solidarity' ; the latter is more consistent with parent-child support patterns.

No abstract