Divergent Genomic and Epigenomic Landscapes of Lung Cancer Subtypes Underscore the Selection of Different Oncogenic Pathways during Tumor Development
Figure 5
Epigenetically altered SqCC genes are significantly enriched for SCLC signaling.
a) SCLC signaling components altered by DNA methylation in SqCC. In this schematic of the SCLC signaling pathway, genes that are hypomethylated and overexpressed are shown in red, and those that are hypermethylated and underexpressed are shown in green. Components at all levels of the pathway are affected, including the transcription factor E2F1, which drives the expression of the oncogenic polycomb group member EZH2. b) EZH2 expression in 58 AC tumors and 53 SqCC tumors. EZH2 expression was assessed in an external dataset, and it was found to be higher, as predicted, in SqCC tumors compared to AC tumors using a Mann-Whitney U test (p<0.0001). c) FHIT differential methylation levels in SqCC and AC tumors. FHIT was shown to be deregulated by both deletion and hypermethylation in a manner that was specific to SqCC tumors. Show here are the differential DNA methylation levels for 30 AC tumors and 13 SqCC tumors. The SqCC tumors are hypermethylated to a much higher degree than the AC tumors, consistent with previous published findings.