In the near future, I will have to deal with circulating cell-free DNA in the context of finding cancer biomarkers - I have read up on methylation, biomarkers, cancer, though I must admit I haven't read too much about cfDNA yet.
In this context, it seems strange that I can't find (450k) methylation data of circulating cell-free DNA.
- Where would I find this kind of data - or why doesn't it exist/isn't it being used?
Can't find is a big thing to say - I have tried several keywords, TCGA does not provide it AFAIK, I have tried on GEO and just by googling. I think GEO returns methylcap/seq data and 27k data for
I would think that if an epigenetic marker is to be used against the background of cfDNA, it would be useful to have a 'universal reference' to test against, instead of finding markers by testing against normal tissue first, and then testing the potential of any/all markers without knowing their status in cfDNA. You don't need to do this when you're trying to find genetic alterations - these 'should' be present in circulating tumor DNA.
Since I'm new to cfDNA I don't know if a universal reference is a good idea, if it's possible, or what the caveats would be.
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Mathias
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I did my PhD on cfDNA back in 2010-2012 where I was looking at copy number alterations and SNPs (in a breast cancer setting). I'm now back in cancer after avoiding it through most of my postdoctoral years, but mainly now focusing on immunotherapy. Epigenetic studies of cfDNA are showing promise in terms of having the ability to infer the tissue of origin of the cfDNA through te analysis of, for example, nucleosome spacing, or indeed methylation patterns. Obviously, by doing this and in addition scanning for mutations in known oncogenes, one could potentially identify where a tumour is beginning to form in the body without the need to perform expensive screens like MRI, or other invasive procedures.
There are indeed not many studies out there for methylation of cfDNA. For next generation sequencing studies on methylation, I found these:
- Identification of tissue-specific cell death using methylation patterns of circulating DNA - unfortunately, they do not appear to have put their data online. You may want to email them. THey also appeared to have used the Infinium microarray, in part.
- Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA - data available HERE
Then there are 3 methylation microarray studies that I found:
- Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer
- Cell-free DNA modification dynamics in abiraterone acetate-treated prostate cancer patients
- Circulating-cell free DNA pooled samples for epigenome-wide discovery of methylation biomarkers for colorectal cancer screening
Best of luck,
Kevin
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