3 research outputs found

    Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

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    Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

    High pathogenicity avian influenza (H5N1) in northern gannets: global spread, clinical signs, and demographic consequences

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    During 2021 and 2022 High Pathogenicity Avian Influenza (HPAI) killed thousands of wild birds across Europe and North America, suggesting a change in infection dynamics and a shift to new hosts, including seabirds. Northern Gannets (Morus bassanus) appeared especially severely impacted, but a detailed account of the data available is required to help understand how the virus spread across the metapopulation, and the ensuing demographic consequences. Accordingly, we analyse information on confirmed and suspected HPAIV outbreaks across most North Atlantic Gannet colonies and for the largest colony (Bass Rock, UK), provide impacts on population size, breeding success, and preliminary results on apparent adult survival and serology. Unusually high numbers of dead Gannets were first noted at colonies in Iceland during April 2022. Outbreaks in May occurred in many Scottish colonies, followed by colonies in Canada, Germany and Norway. By the end of June, outbreaks had occurred in colonies in Canada and the English Channel. Outbreaks in 12 UK and Ireland colonies appeared to follow a clockwise pattern with the last infected colonies recorded in late August/September. Unusually high mortality was recorded at 40 colonies (75% of global total colonies). Dead birds testing positive for HPAIV H5N1 were associated with 58% of these colonies. At Bass Rock, the number of occupied nest sites decreased by at least 71%, breeding success declined by ~66% compared to the long-term UK mean and the resighting of marked individuals suggested that apparent adult survival between 2021 and 2022 could have been substantially lower than the preceding 10-year average. Serological investigation detected antibodies specific to H5 in apparently healthy birds indicating that some Gannets recover from HPAIV infection. Further, most of these recovered birds had black irises, suggestive of a phenotypic indicator of previous infection. Untangling the impacts of HPAIV infection from other challenges faced by seabirds is key to establishing effective conservation strategies for threatened seabird populations as the likelihood of further epizootics increases, due to increasing habitat loss and the industrialization of poultry production
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