These days, everyone wants to stand out. Just look at Lady Gaga and Nicki Minaj—in fact, you can’t not look at them. It turns out that metastatic prostate cancer tumors also stand out from patient to patient, as long as you know where to look.
A team of Johns Hopkins researchers used methyl-binding enrichment and SNP arrays (MBD-SNP) and viewed the data output as a “cityscape” on prostate tumors and found that DNA methylation varied in tumors from different subjects. But, DNA methylation in tumors from the same patient was very similar—suggesting that this modification could actually drive cancer.
Scientists have thought that DNA methylation varies too much to be useful for developing diagnostics or therapies and that the modification wasn’t enough to drive cancer progression.
The team had their doubts, so they developed MBD-SNP and new computational methods to compare genome-wide genetic and epigenetic changes in lethal prostate cancers. MBD-SNP combines an MBD2 pull-down of methylated DNA with hybridization of that DNA to Affymetrix SNP microarrays. Here’s a little of what they learned:
- Tumors from the same person had very similar DNA methylation patterns, which were maintained to the same extent as genetic changes.
- Tumors from different people varied a lot.
- Hypermethylation changes were maintained in the same individual much more often than hypomethylation ones.
- Hypermethylated promoters were more likely to have an association with gene expression than hypomethylated ones.
- Hypermethylated regions had lots of cancer-related genes.
- Cityscape analysis graphically showed that hypermethylated genes tended to cluster in chromosomal “neighborhoods” with other hypermethylated genes.
“There were two major findings that were quite compelling. First, the fact that DNA methylation alterations were maintained to an extent similar to copy number alterations was quite remarkable. Second, the observation that hypermethylation changes, particularly those that correlated with gene expression changes, were highly maintained in all metastases within individuals despite a general tendency to lose normal methylation marks across the genome in those metastases suggests that these changes could be enriched for “driver” epigenetic alterations,” shared Dr. Srinivasan Yegnasubramanian, a Assistant Professor of Oncology at Johns Hopkins.
The researchers say that these data show that personalized medicine may be the way to go for prostate cancer. Also, these modifications “have the potential for producing selectable driver events in carcinogenesis and disease progression,” they say.
Read all the details at Science Translational Medicine, January 2013.