Figure 1 from DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition

Abstract

<p><i>In vitro</i> sensitivity to trametinib in patient-derived DIPG models. <b>A,</b> Oncoprint representation of an integrated annotation of single-nucleotide variants, DNA copy number changes, and structural variants for patient-derived models and tumor biopsy specimens. Samples are arranged in columns with genes labeled along rows. Clinicopathologic and molecular annotations are provided as bars according to the included key. <b>B,</b> The <i>t</i>-statistic–based stochastic neighbor embedding (t-SNE) projection of a combined methylation data set comprising the <i>in vitro</i> models (circled) plus a reference set of glioma subtypes (<i>n</i> = 1,766). The first two projections are plotted on the <i>x</i>- and <i>y</i>-axes, with samples represented by dots colored by subtype as labeled on the figure. <b>C,</b> Drug sensitivities in the mini-screens carried out on cells grown under 2-D and 3-D conditions, visualized by heat map of normalized AUC values. Clinicopathologic and molecular annotations are provided as bars according to the included key. <b>D,</b> Dose–response curves for the MEK inhibitor trametinib tested against patient-derived models <i>in vitro</i> grown in 2-D. <b>E,</b> Dose–response curves for the MEK inhibitor trametinib tested against patient-derived models <i>in vitro</i> grown in 3-D. Cells harboring MAPK pathway alterations are highlighted in blue. Concentration of compound is plotted on a log scale (<i>x</i>-axis) against cell viability (<i>y</i>-axis). Means plus standard errors are plotted from at least <i>n</i> = 3 experiments.</p>

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