Fig. 2

Intra-tumor heterogeneity at the transcriptomic and epigenetic levels. a Molecular heterogeneity (molecular classifications and histo-molecular gradients) of the paired tumor samples and the over-represented pathways linked to cell adhesion and the extracellular matrix are shown in the table. For each patient, the tumor location is indicated (A: apex; B: side wall; C: costo-diaphragmatic; D: highest metabolic site). The molecular classifications into two to four subtypes and the E/S.scores were predicted based on RNA-seq data and are colored in blue or green depending on the subtypes and with a red gradient for the E/S.scores. Pathway over-representation is indicated by a circle with the size and a color proportional to the gene ratio and the FDR p-values, respectively. b, c Based on transcriptome and methylome analysis, the differentially expressed protein coding genes with an associated differentially methylated CpG (DE_DM genes) between paired tumor samples were determined. The percentage of DE_DM genes among all the differentially expressed protein coding genes is shown in the histogram for each patient. The number of DE_DM genes is indicated at the right of the histogram bars (b). The proportion of protein coding genes previously shown to be correlated to the E/S.scores [10] in all DE_DM genes is indicated in the pie charts for patients T227LE and T278HP (c). DE: differentially expressed; DM: differentially methylated