Low-grade prostate cancer diverges early from high grade and metastatic disease.
Bottom Line: Notably, mutations in cancer-associated genes and the p53 signaling pathway were found exclusively in high-grade foci and metastases.The pattern of mutations is consistent with early divergence between low- and high-grade foci and late divergence between high-grade foci and metastases.These data provide insights into the development of high-grade and metastatic prostate cancer.
Affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, USA; Department of Medicine, University of Chicago, Chicago, Illinois, USA.Show MeSH
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Mentions: Rearrangements involving ERG are the most common genetic derangement in prostate cancer and are thought to occur early in tumorigenesis. These events are not typically captured by exome sequencing. Therefore we performed IHC for ERG to look for overexpression, which is typically restricted to cells harboring an ERG rearrangement. Of the two specimens exhibiting positive ERG staining, PrCa 6 showed consistently positive staining in all tumor foci (Fig. 4). In contrast, in PrCa 18 the low-grade focus was negative, the high-grade focus was equivocal with few cells positive for ERG and the metastatic focus was more widely focally positive.
Affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, USA; Department of Medicine, University of Chicago, Chicago, Illinois, USA.