As far as I know, methylation status does not change at recurrence. About 85% of all recurrent tumors have a mesenchymal signature though and this alone makes this a more aggressive tumor. Couple this with surviving treatment resistant cancer cells and the fact that many rGBM tumors are non resectable and the shortened survival time from progression is better understood. Part of the genetic change caused by challenge to the original tumor with resection or other treatment that lead to a mesenchymal phenotype leads to a motility change so that cancer cells are sent off site to create metastasis. This motility signature is able to be intercepted by DCs and acted upon in addition to the findings you shared about increased neoantigen increase and reduced tumor micro environment resistance. Methylation buys time and that time is very important along with all the other factors. Best wishes.
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