Low grade prostate cancer diverges early from high grade and metastatic disease.
Understanding the developmental relationship between indolent and aggressive tumors is central to understanding disease progression and making treatment decisions. For example, most men diagnosed with prostate cancer have clinically indolent disease and die from other causes. Overtreatment of prostate cancer remains a concern. Here we use laser microdissection followed by exome sequencing of low and high grade prostate cancer foci from four subjects, and of metastatic disease from two of those subjects, to evaluate the molecular relationship of coincident cancer foci. Seventy of 79 (87%) high confidence somatic mutations in low grade disease were private to low grade foci. In contrast, high grade foci and metastases harbored many of the same mutations. In cases for which there was a metastatic focus, 15 of 80 (19%) high confidence somatic mutations in high grade foci were private. Seven of the 80 (9%) were shared with low grade foci, and 65 (82%) were shared with metastatic foci. 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. This article is protected by copyright. All rights reserved.
- Profiling Reactive Metabolites via Chemical Trapping and Targeted Mass Spectrometry
- Does the brain listen to the gut?
- (Meta)genomic insights into the pathogenome of Cellulosimicrobium cellulans
- A robust adaptive denoising framework for real-time artifact removal in scalp EEG measurements
- Imputing Gene Expression in Uncollected Tissues Within and Beyond GTEx
- Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break
- Controlling the Cyanobacterial Clock by Synthetically Rewiring Metabolism
- Choosing experiments to accelerate collective discovery
- The transcriptional landscape of age in human peripheral blood
- Digital signaling decouples activation probability and population heterogeneity