help pls: general qs about methylation - (Jun/06/2007 )

Hello, I was hoping to get some information about a few things about methylation. I've tried searching on the internet, but am now abit stuck...

Can anyone shed some light on the following questions and topics, I would be extremely grateful!

Any help would be greatly appreciated. Thanks in advance.

qs1. in which part of tumour progression is methylation involved. ie in which part of the tumour progression timeline is methylation involved. is it an early or late event?

qs2. Tissue specific methylation, do some tissues contain more methylated genes then other tissues? is there such a thing as tissue specific methylation?

qs3. what is the role of methylation in metastasis.

Thanks very much!!

This is my first post. I am currently writing up my Phd thesis...So i thought i would join this friendly forum for help

Thanks again, i look forward to your replies.

Lala.

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Hi Lala,

1. I'm not 100% sure about this, but methylation is something of a well protected imprinted thing. Usually methylation patterns are established early on in embryonic development and are well conserved. I have read a paper, where the authors showed that there was no significant change in methylation status depending on sex and even age! (all kinds of tissues were sampled, an incredible number of CpGs were analyzed, a huge effort).
That information urges me to believe that methylation patterns are already present before the cancer, even enabling it to grow in the first place.

2. Certainly! There are distinct methylation patterns for different kinds of tissues.

3. If metastasis suppressor genes are methylated, this could have an effect on the clinical behavior of tumors.

cheers
Cyburn

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I agree with cyburn with q1.

I believe there are cancer stem cells that already have aberrant methylation and are triggered to expand by some factor that is as yet unknown.

As for tissue specific methylation, have a look at some early global methylation papers using HPLC (back in the 80s) where total methylation was measured from a range of tissues.

Nick

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Thanks so much cyburn, that is really informative!!

and thanks alot methynick!! thats a great help!!

thanks guys. really appreciate it.

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Cyburn: do you have a reference to that article? Sounds interessting to read!

Thanks,

/Molbio

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Well I don't know about cancer, but regarding processes in the brain like memory formation etc. changes in DNA methylation are required and occur througout the whole life span. And not every abberrant methylation is related to imprinting. But (I have no reference for that), I read somewhere that methylation patterns that survive meiosis are less likely to be deleted later on?
On the other hand there are also some reports (again, have to search the reference, I think it's Szyfs group) showing a rapid loss of methylation patterns in rats directly after birth and a slower rebuilding of distinct patterns throughout the first days-weeks of the newborn.

For cancer, just coming to my mind - some carcinogens are known to influence the DNA methylation - and thereby changing the activity of oncogenes and tumor supressor genes. So I am also not too sure about cancer stem cells. But that are just my two cents...
Krümel

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Thanks Krümel, thats really interesting stuff!!



This is a really cool message board. I am glad i joined up

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for your #1, I've seen methylation occur quite early before cancer has appeared. We have difficulty sampling normal in cancer patients, because adjacent normal is quite intermediately methylated. Most of our research suggests that methylation changes occur as a precursor to tumor formation.

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