Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma

Cancers
Huiyuan ZhangAkash J Patel

Abstract

Meningiomas constitute one-third of all primary brain tumors. Although typically benign, about 20% of these tumors recur despite surgery and radiation, and may ultimately prove fatal. There are currently no effective chemotherapies for meningioma. We, therefore, set out to develop patient-derived orthotopic xenograft (PDOX) mouse models of human meningioma using tumor. Of nine patients, four had World Health Organization (WHO) grade I tumors, five had WHO grade II tumors, and in this second group two patients also had recurrent (WHO grade III) meningioma. We also classified the tumors according to our recently developed molecular classification system (Types A, B, and C, with C being the most aggressive). We transplanted all 11 surgical samples into the skull base of immunodeficient (SCID) mice. Only the primary and recurrent tumor cells from one patient-both molecular Type C, despite being WHO grades II and III, respectively-led to the formation of meningioma in the resulting mouse models. We characterized the xenografts by histopathology and RNA-seq and compared them with the original tumors. We performed an in vitro drug screen using 60 anti-cancer drugs followed by in vivo validation. The PDOX models established from the pr...Continue Reading

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Citations

Mar 22, 2021·Experimental and Molecular Pathology·Juliana Cristina de SouzaCarolina Cavaliéri Gomes
Mar 23, 2021·Frontiers in Immunology·Darel Martínez BedoyaDenis Migliorini
Jul 25, 2021·Journal of Clinical Medicine·Philip D TatmanD Ryan Ormond
Aug 8, 2021·Cancers·Julien BoettoMichel Kalamarides
Jul 3, 2021·Neuro-oncology·Shintaro YamazakiAtsushi Natsume

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Methods Mentioned

BETA
xenograft
xenografts
electrophoresis
PCR
chip

Software Mentioned

Excel Solver
TopHat
FastQC
GraphPad
GraphPad Prism
DESeq2
HTseq

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