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.
We provide evidence of how RAD51AP1 can be of importance as potential biomarker since it is overexpressed in both tissue and peripheral blood of ovarian and lung cancer patients. Silencing of the gene can also lead to decrease in cell proliferation in vitro, so a potential therapeutic target.
A detailed network describing asparagine metabolism in plants was constructed using published data from Arabidopsis (Arabidopsis thaliana) maize (Zea mays), wheat (Triticum aestivum), pea (Pisum sativum), soybean (Glycine max), lupin (Lupus albus), and other species, including animals. Asparagine synthesis and degradation is a major part of amino acid and nitrogen metabolism in plants. The complexity of its metabolism, including limiting and regulatory factors, was represented in a logical sequence in a pathway diagram built using yED graph editor software. The network was used with a Unique Network Identification Pipeline in the analysis of data from 18 publicly available transcriptomic data studies. This identified links between genes involved in asparagine metabolism in wheat roots under drought stress, wheat leaves under drought stress, and wheat leaves under conditions of sulfur and nitrogen deficiency. The network represents a powerful aid for interpreting the interactions not only between the genes in the pathway but also among enzymes, metabolites and smaller molecules. It provides a concise, clear understanding of the complexity of asparagine metabolism that could aid the interpretation of data relating to wider amino acid metabolism and other metabolic processes.
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