Abstract 3839: Investigation of epigenetic based inter-tumoral heterogeneity identifies novel ZMIZ1 gene as a biomarker of cancer patient survival in multiple tumor types

Glioblastoma is the most malignant primary brain tumor and is universally fatal despite the use of the best treatment available. However a small percentage of these patients live considerably longer. Extensive genetic and epigenetic analysis has identified IDH1 mutation, G-CIMP (Glioma-CpG Island Methylator Phenotype) phenotype and MGMT as markers of better survival in glioblastoma. These markers though can only be associated with a small fraction of long term survivors (defined as glioblastoma patients surviving >3 years), underlying the need for better biomarkers of improved survival. Epigenetic analysis of inter-tumoral heterogeneity in the TCGA glioblastoma cohort identified a truncated form of the novel ZMZI1 gene to be associated with improved survival in patients hypermethylated in the alternative promoter of the truncated ZMIZ1 form, in an independent manner from IDH1, G-CIMP or MGMT methylation status.A validation cohort of 31 glioblastoma long term survivors with low prevalence of the known markers IDH1, G-CIMP and MGMT showed that ZMIZ1 methylation was positive in 42% of the patients, more sensitive and specific than IDH1, G-CIMP or MGMT. Extending our analysis to lower grade gliomas as well as other central nervous system tumors showed that higher methylation of the truncated ZMIZ1 was predicting a more favorable outcome in astrocytomas but not in oligodendrogliomas. Furthermore, in non-CNS tumors including breast cancer, colorectal cancer, bladder cancer and rena...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research