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. 2019 Nov 7;10:5061. doi: 10.1038/s41467-019-13002-x

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — p53^C accelerates spontaneous tumorigenesis and gliomagenesis in mice. a Survival of p53 polymorphic mice. P < 0.0001 (log-rank test). b Hematoxylin and eosin stain (H&E) staining of representative follicular lymphoma (FL) and splenic marginal zone lymphoma (SMZL) in polymorphic mice. Scale bar = 200 μm (top), 20 μm (bottom). c Diffuse large B-cell lymphoma (DLBCL, top) and histiosarcoma (bottom). Scale bar = 20 μm. d Immunohistochemistry (IHC) staining for B-cell marker B220 in FL and SMZL. Scale bar = 200 μm (top), 20 μm (bottom). e IHC staining for Ig κ light chain of SMZL. Scale bar = 200 μm (top), 50 μm (bottom). f Survival of polymorphic mice injected in the right subventricular zone (SVZ) with retrovirus carrying Pdgfb. P < 0.0001 (log-rank). g H&E of glioma in p53^C/C mice (n = 9). 1, a representative tumor (magnification 2 × ). Scale bar = 1 mm. 2, invasive growth of the tumor cells. Arrows showing invasion front of the tumor. Scale bar = 100 μm. 3, a blood vessel (arrows) in the tumor tissue (×1000). 4, infiltrating monocytes (arrow) within tumors. 5, Necrotic tumor cells (Arrows). 6, highly invasive tumor cell (arrows) growth surrounding a neuron (star). Scale bar = 5 μm in 3–6. h IHC for the astrocyte/glial cell marker GFAP. Arrow showing a tumor cell staining positive for GFAP, but most tumor cells lost GFAP expression. i IHC of synaptophysin. Scale bar in (h, i) = 100 μm (left), 10 μm (right). j IHC of glioma stem cell markers in p53^C/C mice. Pdgfb was tagged with 3× hemagglutinin (HA). PCNA: tumor cell proliferation, GD3, Nestin, and Oligo2: neuralgia progenitor/glioma stem cell maker (red arrows point to the accumulation of GD3 at invasive front line; blue arrow: necrotic cells). Scale bars = 1 mm (top), 100 μm (middle), and 5 μm (bottom row). k IHC of other markers in p53^C/C mice. Green arrow: GFAP-positive cell with typical astrocyte morphology, red arrow: GFAP-positive tumor cell. Scale bars = 100 μm (top), 20 μm (middle), and 5 μm (bottom). N normal tissues, T tumors. Images were representative of staining six tumors (one per animal) (g–k). l Survival of syngeneic WT mice orthotopically transplanted with p53^C/C glioma cells (f). P = 0.003 (log-rank)