How can one report the result of an assay on global DNA methylation done using an ELISA based technique.
It response to the titles question its is important to know your baseline for this. We can tell whether a gene is methylated or not but that wont give us information as to whether that represents a healthy/normal state for that gene. Its important to remember that methylation is a normal and necessary part of our make up and we get ranges of methylation in different tissues.
If we wanted to use methylation clinically we need to get a baseline for the 'normal' population, whether that is global to the tissue or specific genes in question and from there we can look at the methylation states of diseased/unhealthy populations and can build predictive models around that for unknown samples. These outputs can totally be in a range or absolute cut offs and can infer increased risk of a certain disease etc. In other words, yes, its important to have a baseline to make a clinical interpretation of anything.
There is basically no reference range for a "normal" DNA methylation. All depends where the methylation is (promoter region,exons, introns, CpG islands etc).
DNA methylation is a critical phenomenon for normal development to regulate the function of the cells/tissue. There is no fixed point for the process. You need the understand the function of the target in normal and disease conditions, which got methylated or unmethylated.
If a gene X is METHYLATED in CANCER then mostly it may have an ANTI-CANCER function. However, gene X is UMETHYLATED in CANCER then probably it may have a PRO-CANCER function.
Similarly, a gene is methylated in normal/healthy condition then it means the gene has no function at that moment but you may see a change in the methylation status of the same gene in disease condition OR VICE VERSA.
Hi Saurabh Mandal, just on your point " If a gene X is METHYLATED in CANCER then mostly it may have an ANTI-CANCER function", this isnt the case. Methylation is provided by the DNMT family on enzymes that provide regulatory and novel methylation in the cell but as of yet do so in a more random fashion (novel) or methylate hemi-methylated DNA (regulation). In cancer, whether spontaneous through mutilations or driven through viral vectors like HPV the methylation acquired is random. When we hit the point where the cell becomes cancerous then yes there is methlyation in anti-cancer genes but also in a host of other genes and seeing as we have cancer then there is little methylation in pro-oncogenic genes.
We cant say because X gene is methylated that it has anti cancer effects.
There has been some evidence of semi-targeted methyltion in HPV 16 infections but more akin to preferential binding of particular sequences when DNMT binds with some of HPV 16's oncogenic proteins
Also in the normal state a methylated gene has reduced function (depending if one or both copies are methylated) but this can be reversed by the TET enzymes and others as part of normal cellular control, not just cancer or disease.
Hope that has been some help
Welcome Saurabh Mandal, though you are correct to a point, we do generally pick genes with some anti cancer effects for specific methylation detection tests, but at a global level its less so
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