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Activity Number: 370
Type: Contributed
Date/Time: Tuesday, August 2, 2016 : 10:30 AM to 12:20 PM
Sponsor: ENAR
Abstract #321434
Title: Patient-Derived Model Systems: Design Considerations for Pre-Clinical Study
Author(s): Laila M. Poisson* and Hoon Kim and Mary Winn and David Cherba and Claudius Mueller and Emmanuel F. Petricoin and Roeland Verhaak and Tom Mikkelsen and Ana deCarvalho
Companies: Henry Ford Health System and MD Anderson Cancer Center and Van Andel Research Institute and Van Andel Research Institute and George Mason University and George Mason University and MD Anderson Cancer Center and Henry Ford Health System and Henry Ford Health System
Keywords: pre-clinical trial ; variability ; glioblastoma ; sequencing

In a study of thirteen patient derived models of glioblastoma (GBM), we explored the genomic and phenotypic characteristics of the tumors relative to their derived in vitro cell spheroids and in vivo intra-cranial tutor implant(s) (triplicate). Low-pass whole-genome sequencing, whole exome sequencing, RNA sequencing, and reverse phase protein array (RPPA) assays were performed. Data were assessed for changes between models - both individual molecular features and pathways. The 13 tumors are representative of the diversity in the patient population of GBM. Though mutation frequency tended to increase in the models, key mutation and copy number alterations were retained. Phenotypic alterations in gene and protein regulation demonstrated effects of tumor environment, yet drug target predictions were fairly consistent. Though we see good correlation within tumor lines, there is much variability between lines, demonstrated molecularly and through survival studies. These biological findings provide the building blocks for generalizable preclinical trials, especially with regard to intra-line correlation and inter-line variability. Data will be made available upon publication.

Authors who are presenting talks have a * after their name.

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