Journal: BMC Genomics

Article Title: Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial–mesenchymal transition

doi: 10.1186/1471-2164-15-1079

Figure Lengend Snippet: Specific SRAM methylation patterns define epithelial (E) and mesenchymal (M) cell types. A) Hierarchical clustering of SRAMs for a subset of cell lines (n = 47) with RPPA data for E-cadherin (ECAD) segregates cell lines into high and low ECAD groups. Representative genes that are preferentially unmethylated ( AXL ) or methylated ( CDH1 , SPINT1 ) in the mesenchymal cells are shown. Illumina gene expression levels of EMT markers ( ZEB1 , Vimentin ( VIM ), Twist1 , Fibronectin ( FN1 ), CDH2 , and CDH1 ) are overlaid to confirm the E vs M identity of the cell lines. B) Wilcoxon rank sum test was used to identify the SRAMs that are differentially methylated between E and M cells, which we call the EMT-SRAMs. The identified 135 probes (111 unique genes) were used for hierarchical clustering of the cell lines. EMT-SRAMs that are predominantly methylated in M cells are called M-SRAMs, and those methylated in E cells are called E-SRAMs. C) EMT-SRAM association with EMT network genes using curated network analysis. Closest second neighbor analysis of genes associated with core EMT factors (“EMT Hub genes”: CDH1, CDH2, FN1, SNAI1, SNAI2, GSC ) finds numerous associations with genes within the EMT-SRAM set. Red spheres represent SRAMs that are methylated in M cells; green spheres are those methylated in E cells; white spheres represent linking genes.

Article Snippet: Illumina gene expression levels of EMT markers ( ZEB1 , Vimentin ( VIM ), Twist1 , Fibronectin ( FN1 ), CDH2 , and CDH1 ) are overlaid to confirm the E vs M identity of the cell lines.

Techniques: Methylation, Gene Expression

Journal: BMC Genomics

Article Title: Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial–mesenchymal transition

doi: 10.1186/1471-2164-15-1079

Figure Lengend Snippet: Extent of methylated SRAMs associated with erlotinib response in cell lines and patients in BATTLE-1 trial. A) Hierarchical clustering of EMT-SRAMs in 52 wild-type (WT) EGFR NSCLC cell lines, with erlotinib IC50 levels overlying individual cell lines. G1 and G2 represent the two cell lines clustered by SRAM methylation. KRAS mutant cells are represented by asterisks. B) Erlotinib IC50 values of G1 vs G2 clusters for the combined cell lines, and the WT EGFR/KRAS cells. G2 cluster had significantly higher IC50 values than G1 cluster. Error bars indicate average and 95% confidence interval. C) Hierarchical clustering of expression of SRAMs in the panel of cell lines with RPPA data for E-cadherin (49) clusters of E and M cells. Specific gene markers that relate to EMT are on the right. D) Hierarchical clustering based on first principle component analysis (PCA) of SRAM expression signature in the tumor biopsies from patients in BATTLE-1 trial clusters tumors into groups that resemble the separation seen in the cell lines. E) Eight-week disease control (DC) of patients treated with erlotinib or sorafenib based on the first PCA separation. EGFR mutant tumors were excluded.

Article Snippet: Illumina gene expression levels of EMT markers ( ZEB1 , Vimentin ( VIM ), Twist1 , Fibronectin ( FN1 ), CDH2 , and CDH1 ) are overlaid to confirm the E vs M identity of the cell lines.

Techniques: Methylation, Mutagenesis, Expressing, Control