Figure 6.
GBM-specific expression of an alternate transcript from a hypomethylated promoter in the TERT gene body. (A) GBM individual hypomethylated DMRs (Q < 10−5) within a ∼3.4-Mb region that is recurrently amplified in breast cancer and is enriched by GREAT analysis of recurring and individual hypomethylated DMRs. The location of the breast cancer copy number amplicon is shown in gray at the bottom. (B) GBM hypomethylation at a TERT gene body promoter, which is located near the glioma risk SNP rs2736100. GBMs 1, 2, and 4 had hypomethylated DMRs (Q-values are 10−14, 10−14, 10−21). (C) Infinium HumanMethylation450 array data for two CpGs in the recurrent hypomethylated DMR at the Delta TERT promoter. (Gray points) 126 TCGA-assayed GBMs. (Black triangles) TCGA normal brain. The percentage of GBMs at each CpG with methylation <80% (red line) is shown in red text. (D) Delta TERT mRNA isoform abundance quantified by qRT-PCR. Fold expression ± SD relative to the average of two normal brains is graphed. (NB) Normal brain. (FNSC) Cultured fetal neural stem cells. (U87) GBM cell line. (GBM5 cult.) Short-term serum-grown culture of GBM 5. (E) Detection of the transcription initiation site within the TERT hypomethylated gene body by 5′-RACE.