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BC progression model recapitulates hypermethylation events associated w/premalignacy

Re: BC progression model recapitulates hypermethylation events associated w/premalig

Wow. 44 pages of propeller spinning fun. Ok..I only read the page count.
Skipping to the conclusion:

Quote:

Conclusions
Cells without p16 function are resistant to arrest induced by ras-associated oncogenic stress. The accelerated accumulation of genetic and epigenetic events dictate their ability to bypass additional arrest signals allowing rare emergent subpopulations to immortalize, and grow in soft agar. We have identified a multigene methylation pattern acquired during this in vitro progression to malignancy that is detected in vivo in both premalignant and malignant lesions.
This model will thus allow further study of the mechanisms underlying the accumulation of epigenetic alterations that occur during progression to malignancy. By characterizing the methylation profiles that manifest at different stages of transformation, biomarkers with diagnostic and/or prognostic value could eventually be identified.

Re: BC progression model recapitulates hypermethylation events associated w/premalig

Here is a recap (from a non-scientist) of the stuff you skipped:

The researchers looked at samples of breast tissue taken from healthy breasts (reduction surgery), cancerous breasts (DCIS & IDC) and hyperplasia, both typical and atypical. What they found was two specific genes (RASSF1A, involved in cell cycle regulation, and SFRP1, involved in cell signaling) which become methylated in an epigenetic alteration (that is, an alteration which can be "switched" on and off) and that concomittant metylation of both appears to be one of the earliest steps in initiating breast cancer. They found evidence of the dual methylation in almost all of the DCIS, IDC and atypical hyperplasia, and in virtually none of the healthy tissue. The authors said (on page 19) "Interestingly, transient alteration in the cellular environment can permanently alter cell behavior," observing that once immortalized, the unstable cells no longer required sustained stimulation (via a transient change) to proliferate, suggesting that the initial, transient signaling led to additional alterations that were adequate for the cells to maintain independent growth.

The reason I think this is important is because it says the way we have been looking for the "smoking gun" that causes breast cancer (some kind of permanent genetic change or abberation) is incorrect, and we are not likely to find it and should begin looking at other causes. To demonstrate in the lab that the fundamental change that causes bc can be transient and fleeting is a big step, and goes further to explain why so many women with few or no risk factors for bc go on to develop the disease.

Hopeful

Re: BC progression model recapitulates hypermethylation events associated w/premalig

It's much better now with English subtitles ;)