TMOD-02. DIFFUSE GLIOMATOSIS IN MOUSE MODEL OF GFAP TISSUE SPECIFIC KNOCK IN OF EGFRvIII AND KNOCK OUT OF p19 ARF. (5th November 2018)

• Record Type: Journal Article
• Authors: Li, Mira; Agnihotri, Sameer; Wilson, Mark; Metcalf, Julie; Singh, Olivia; Karimi, Shirin; Burrell, Kelly; Bunda, Severa; Suppiah, Suganth; Aldape, Kenneth; Zadeh, Gelareh
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi268
• Page End: vi268
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.1115
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: We generated a transgenic mouse harboring EGFRvIII knock in and homozygous p19 ARF deletion restricted to glial cells. The mice developed diffuse glioma with some tumors showing classical histological pseudopalisading necrosis and hyper vascularity. Transgenic mice develop tumors as early as 1 month and 53% of mice die by 6 months of age. MRIs reveal that mice develop ventriculomegaly and external hydrocephalus when tumor cell infiltration grows exophytic and presents with accumulations of neoplastic cells in association with leptomeninges, in addition to the brain and spinal cord parenchyma. Immunohistochemical analysis shows a strong glial component; tumors display positive GFAP, S100 staining and negative NeuN, synaptophysin staining. Three primary cell cultures were isolated as adherent and neurospheres from mice with tumors. During in vitro culture, EGFRvIII expression was lost in 2 of 3 lines, similar to seen in humans GBMs. Results were confirmed by Western blot and RT-PCR. Intracranial injection with EGFRvIII positive lines resulted in tumors in NODSCID mice. Immunohistochemistry staining of xenografts show that cells retained EGFRvIII expression, thus reinforcing that the importance of tissue microenvironment in maintaining genomic drivers. We present phenotype and genomic profile of a new transgenic model of glioma, with a prominent phenotype of leptomeningeal spread, potentially serving as a model for this important manifestation of human tumors.