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Fig. 7 | Genome Biology

Fig. 7

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

Fig. 7

Novel context-dependent differential tumor suppressive effects of Pten in the brain and spinal cord. a Brain and spinal gliomas share a core set of drivers. Upper Venn diagram shows the top genes from each tumor cohort, with core drivers including genes such as Cdkn2a, Pten, and Sox6. Lower Venn diagram shows among all transposon CIS genes, brain and spinal cord tumors share 206 genes (with at least one insertion in each tumor type), and there are 35 brain glioma-specific CIS genes and 40 spinal glioma-specific CIS genes. b Bar plot comparing number of insertions between brain and spinal tumors for the top 10 CIS genes. Cdkn2a, Ppp1r14c, and Pten have significantly more insertions (normalized for number of tumors analyzed) in spinal than brain tumors, and Sox6 has more insertions in brain tumors (Fisher’s exact test, p < 0.05). c All Pten piggyBac insertions from brain gliomas and spinal cord gliomas are plotted across the structure of the gene, with the pattern implying disruption; note the higher density of insertions in this gene in spinal cord tumors. d Conditional mice with both EGFRvIII and Pten heterozygous loss (exons 4 and 5 deleted with cre [82]) were generated and monitored for brain and spinal tumor development. e Pten loss significantly shortened survival time of mice in the context of conditional EGFRvIII expression (p < 0.0001, log-rank test, n = 11 EGFRvIII; nes-cre; Pten+/− mice and n = 48 EGFRvIII; nes-cre mice). f EGFRvIII; nes-cre; Pten+/− spinal tumor growth and nerve root invasion. Left panels: cervical and thoracic spinal cord with encasement by tumor cells growing within the subarachnoid space. Middle panels: detailed view of the spinal cord and tumor cells. Right panels: tumor cells invading root structures. Scale bar corresponds to 0.8 mm for left upper panel and 1.6 mm for left lower panel, and 180 μm for all other panels. g Histological assessment of EGFRvIII; nes-cre; Pten+/− tumors. In the brain, lesions were predominantly microneoplasias (tumor precursors) rather than fully formed gliomas; in contrast, in the spinal cord, gliomas were uniformly fully established and grade II. h Illustration showing the tumor tissue-of-origin in the CNS influences Pten tumor suppressive effect strengths

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