Journal article

A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma

Jacqueline P Whitehouse, Meegan Howlett, Hilary Hii, Chelsea Mayoh, Marie Wong, Paulette Barahona, Pamela Ajuyah, Christine L White, Molly K Buntine, Jason M Dyke, Sharon Lee, Santosh Valvi, Jason Stanley, Clara Andradas, Brooke Carline, Mani Kuchibhotla, Paul G Ekert, Mark J Cowley, Nicholas G Gottardo, Raelene Endersby

Cancers | MDPI | Published : 2020

Abstract

Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression sugg..

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Grants

Funding Acknowledgements

This research was funded by The Pirate Ship Foundation. DNAmethylation arrays were partially funded through the AIM-BRAIN PROject, an ANZCHOG clinical trial funded by Robert Connor Dawes Foundation, Carrie's Beanies 4 Brain Cancer and Cancer Australia, and the Victorian Government's Operational Infrastructure Support Program. M.J.C. has support from Cancer Australia, My Room, NSW Ministry of Health funded Luminesce Alliance, R.E. has support from the John Lillie Cancer Research Fellowship and Brainchild Fellowship, N.G.G. is supported by a Cancer Council of Western Australia Fellowship and the Stan Perron Chair of Paediatric Haematology and Oncology, J.S. was supported by a Cancer Council of Western Australia Vacation Scholarship.