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Series GSE72732 Query DataSets for GSE72732
Status Public on Dec 19, 2016
Title Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma [SNP]
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
SNP genotyping by SNP array
Summary Purpose: Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors.
Experimental Design: Here, we used 33 single cell–derived subclones generated from five clinical glioblastoma specimens for exploring intra- and interindividual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacologic sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors.
Results: Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential antiglioblastoma compounds. A more comprehensive intratumoral analysis revealed that stable genetic and phenotypic characteristics of coexisting subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacologic profiles could be shown for establishing rational strategies for individualized secondary lines of treatment.
Conclusions: Our data provide a previously unrecognized strategy for revealing functional consequences of intratumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma
Overall design SNP profiling of 7 cultured glioblastoma-samples from one surgical specimen. 5 subclones (GNV019_CL1/2/3/6/7) were derived from a parental culture (GNV019; in an early (3) and late (10) passage).
Contributor(s) Reinartz R, Scheffler B
Citation(s) 27521447
Submission date Sep 04, 2015
Last update date Dec 21, 2016
Contact name Roman Reinartz
Organization name University of Bonn
Department Institute of Reconstructive Neurobiology
Lab Stem Cell Pathologies Group
Street address Sigmund Freud Strasse 25
City Bonn
ZIP/Postal code 53127
Country Germany
Platforms (2)
GPL8887 Illumina Human610-Quad v1.0 BeadChip
GPL20886 Illumina HumanHap550-Duov3 Genotyping BeadChip (HumanHap550-2v3_B; Name version)
Samples (7)
GSM1869262 GNV019_p3
GSM1869263 GNV019_p10
GSM1869264 GNV019_CL1
BioProject PRJNA294783

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72732_RAW.tar 204.0 Mb (http)(custom) TAR (of IDAT)
GSE72732_non_normalized.txt.gz 52.5 Mb (ftp)(http) TXT
Processed data included within Sample table

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