Harnessing Autopsied DIPG Tumor Tissues for Orthotopic Xenograft Model Development in the Brain Stems of SCID Mice
Final rept. 15 Aug 2011-14 Aug 2012
BAYLOR COLL OF MEDICINE HOUSTON TX
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Diffuse intrinsic pontine glioma DIPG remains the most lethal childhood cancer. The slow progress in biological study and preclinical drug development is caused by the lack of fresh tumor tissues and clinically relevant animal models. The objective of our proposal is to determine if autopsied DIPG tissues can be used to develop orthotopic intra-brain stem xenograft mouse models that will replicate the biology of the original patient tumors. Through a series of studies, we demonstrated that a small percentage approximately 10 of DIPG tumor cells can survive the long-term post-mortem period of hypoxiaanoxia and starvation and that the surviving tumor cells can form new xenograft tumors in the brain stems of SCID mice. We further demonstrated that the xenograft tumors replicate key histopathological features of the original patient tumors, and the cohort of animal models can be expanded through serial subtransplantations in vivo in mouse brain stems. We also completed the whole genome expression in 2 models and finished the whole exon sequencing in 4 DIPG tumors and identified a subset of novel dysregulated and mutated genes. Our results provide a new concept that can potentially revolutionize the use of autopsied tumor tissues for biological and preclinical studies of latelethal stage of human cancers.
- Medicine and Medical Research