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Fig. 1 | Genome Biology

Fig. 1

From: PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas

Fig. 1

EGFRvIII initiates gliomagenesis in the brain and spinal cord of mice. a Outline of the experiment: EGFRvIII was conditionally expressed throughout the central nervous system using nes-cre. b Structures of EGFRvIII [12] and nes-cre alleles. Notation: CAG = cytomegalovirus (CMV) early enhancer, chicken β-actin promoter; pA = poly-adenylation signal; red triangle = loxP site; hGH(pA) = human growth hormone polyadenylation signal; nestin enhII = enhancer in second intron of rat nestin gene [27]. c Kaplan-Meier plot of EGFRvIII; nes-cre mice and control (nes-cre) mice (p < 0.0001, log-rank test, n = 48 and n = 10 mice respectively). d Low- and high-power views of a small glioma (microneoplasia) protruding from the cortical surface of the brain. Scale bar corresponds to 90 μm for left panel and 25 μm for right panel. e Pie charts show proportions of brain and spinal tumors of various grades in heterozygous EGFRvIII; nes-cre mice. f Pie charts show relative proportions of Ki67 proliferative index for brain and spinal tumors of these mice. g Top panel (left to right): low-power view of H&E stain of a brain with a typical microneoplasia (same as in d), and high-power view of immunostains of this neoplasm showing positivity for neural lineage markers double-cortin (DCx), GFAP (reflecting reactive astrocytes between tumor cells), Olig2, Sox2, and PDGFRa (n = 5/5). Histopathologic diagnosis was made by an expert consultant neuro-oncological pathologist. Lower panel (left to right): low-power view of spinal cord with an encasing glioma, and high-power views of immunostains of this tumor for neural lineage markers—tumor cells are negative for DCx, reactive astrocytes are positive for GFAP, and tumor cells are positive for Olig2, Sox2, and PDGFRa. Scale bar corresponds to 1 mm for left H&E panel, 70 μm for upper immunostain panels; 0.7 mm for lower H&E panel, 140 μm for lower immunostain panels

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