The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.

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Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day 1,2 despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biologic effect 3. The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischemic injury 4,5. Here we examined the mechanistic basis for cell therapy in mice after ischemia/ reperfusion (I/R) injury, and while heart function was enhanced, it was not associated with new cardiomyocyte production. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2 + and CX3CR1 + macrophages. Intra-cardiac injection of 2 distinct types of adult stem cells, freeze/thaw-killed cells or a chemical inducer of the innate immune response similarly induced regional CCR2 + and CX3CR1 + macrophage accumulation and provided functional rejuvenation to the I/R-injured heart. This selective macrophage response altered cardiac fibroblast activity, reduced border zone extracellular matrix (ECM) content, and enhanced the mechanical properties of the injured area. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: