Author:
Meyer Mona,Reimand Jüri,Lan Xiaoyang,Head Renee,Zhu Xueming,Kushida Michelle,Bayani Jane,Pressey Jessica C.,Lionel Anath C.,Clarke Ian D.,Cusimano Michael,Squire Jeremy A.,Scherer Stephen W.,Bernstein Mark,Woodin Melanie A.,Bader Gary D.,Dirks Peter B.
Abstract
Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies.
Publisher
Proceedings of the National Academy of Sciences
Cited by
323 articles.
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