Recent surprising evidence has shown that metastatic tumors usually do not vary in their genomes within an individual. Yet, these tumors behave differently at different sites around the body. Does that mean that epigenetic profiling will be too variable to target for cancer treatment? In a word, no.
Martin J. Aryee et al., from Johns Hopkins, have published their work in DNA Methylation Alterations Exhibit Intraindividual Stability and Interindividual Heterogeneity in Prostate Cancer Metastases in Science Translational Medicine. They looked at methylation signatures, including total methylation and allele-specific methylation (ASM) in lethal metastatic prostate cancer, among tumors from 24 donors. Methylated DNA was enriched from the genomic DNA using a Methyl-CpG Binding Domain (MBD) -based capture. Their MBD-SNP assay provided total methylation, ASM and copy number concurrently for each sample. Microarray analysis and computational analysis were used downstream to produce “cityscapes” of visualized data.
The epigenetic and genetic data varied a lot among the individual donors. Yet intriguingly, static epigenetic profiles were seen among metastatic tumors for each individual donor. This means that although metastatic prostate cancer tumors are somehow able to overcome treatments like the removal of androgens (surgical or medical castration), there are still “non-moving” epigenetic biomarkers targets to aim at to develop new treatments. The authors point out that it will be important to distinguish between the driver and passenger DNA methylation alterations in carcinogenesis. So there’s all that to still sort through in functional studies to determine targets with casuality in the disease progression. The stable methylomes within individuals supports the goals of personalized medicine in prostate cancer treatment – so it’s definitely worth the effort.
Aryee MJ, Liu W, Engelmann JC, Nuhn P, Gurel M, Haffner MC, Esopi D, Irizarry RA, Getzenberg RH, Nelson WG, Luo J, Xu J, Isaacs WB, Bova GS, & Yegnasubramanian S (2013). DNA methylation alterations exhibit intraindividual stability and interindividual heterogeneity in prostate cancer metastases. Science translational medicine, 5 (169) PMID: 23345608