Research ArticleCancer

DNA Methylation Alterations Exhibit Intraindividual Stability and Interindividual Heterogeneity in Prostate Cancer Metastases

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Science Translational Medicine  23 Jan 2013:
Vol. 5, Issue 169, pp. 169ra10
DOI: 10.1126/scitranslmed.3005211

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Surveying the DNA Methylation “Cityscape” of Prostate Cancer

Alterations in DNA methylation are a hallmark of human cancers, including prostate cancer. Understanding which of these alterations “drive” cancer initiation, progression, and metastasis, and which of these are merely “passengers” not involved in the chain of causation, is a major translational challenge. To tackle this challenge in the context of metastatic prostate cancer, Aryee et al. carried out genome-scale analyses of DNA methylation alterations in multiple metastases from each of 13 men who had died of metastatic prostate cancer. To visualize both the frequency of each methylation alteration in the metastases and the consistency with which each alteration was maintained across all metastases from an individual, the authors created DNA methylation “cityscape” plots. These analyses revealed that each individual developed a unique DNA methylation signature that was largely maintained across all metastases within that individual. Additionally, a set of DNA “hypermethylation” alterations, defined as regions that were normally unmethylated but acquired cancer-specific DNA methylation, were enriched for prostate cancer “drivers.” Such DNA hypermethylation alterations are attractive potential targets for development of longitudinal markers and therapeutic strategies for prostate cancer management.