Development of robust in vitro and in vivo preclinical models for diffuse intrinsic pontine glioma


June 18, 2016
Yadavilli S, Yang X, Kilburn L, Kilburn L, Magge S, Kambhampati M, Waanders A, Han H. Muellar S, Resnick A, Packer R, Nazarian J


Diffuse intrinsic pontine glioma (DIPG) is a tumor of the brainstem arising in the pons. Because of the critical anatomical location total surgical resection of the tumor is not amenable. However, recently, upfront biopsies are being obtained in order to assist in genome-informed treatment modalities. We and others have recently identified obligate genomic mutations responsible for DIPG tumorigenicity. This study aims to generate robust in vitro and in vivo preclinical models that represent main obligate partner DIPG mutations using the autopsy (CNHS IRB # 1339) and rare upfront biopsy (Pacific Pediatric Neuro-oncology Consortium protocol-003) specimens. Postmortem tissue processing resulted in generation of three primary DIPG lines and three corresponding (orthotopically injected) in vivo models. Specimen obtained at biopsy, resulted in generation of two DIPG primary lines. Biopsies from all patients (n = 11) have been orthotopically injected awaiting tumor development. Establishing subtype specific preclinical DIPG models representing various DIPG molecular subtypes (obligate partner mutations) will allow for robust and rapid preclinical testing targeting DIPG tumorigenesis. To empower pre-clinical use of the developed resources, cell-lines and associated phenotypic and genomic data will be integrated and available via a data visualization and request portal.