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Imaging Genomic mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma
Multiforme
PO Zinn1, B Mahajan2, P Sathyan1, S Singh1, S Majumdar1, A Flanders3, E Huang4, R Jain5, D Gutman6, S Hwang6, J Kirby7, J Freyman7, TCGA Glioma Phenotype Research Group, , F Jolesz2, RR Colen2,
1 M.D. Anderson Cancer Center, Houston, TX, USA.2 Brigham and Women's Hospital, Boston, MA, USA.3 Thomas Jefferson University Hospital, Philadelphia, PA, USA.4 National Cancer Institute, Bethesda, MD, USA. 5 Henry Ford, Detroit, MI, USA. 6 Emory University, Atlanta, GA, USA. 7 SAIC-Frederick, Bethesda, MD, USA.
• Imaging genomics has emerged as a new field which links the specific imaging traits (radiophenotypes) with gene-expression profiles.
• We present our paper on the first comprehensive imaging genomic analysis using quantitative MRI volumetrics and large scale gene- and micro-RNA expression profiling in GBM.
• This was first described by our group (Zinn et al PLOSOne 2011) in 2011 where an invasive gene and microRNA was uncovered using the FLAIR volume as an MRI biomarker (radiophenotype).
In this presentation, we seek to demonstrate the imaging-genomic mapping of an invasive MRI radiophenotype, linking MR imaging traits with gene- and miRNA expression profiles, in GBM patients to determine genomic correlates of an edema/invasion MRI radiophenotype
In order to:- DiscoverDiscover new genomic targets for GBM treatment (decreasing
edema/invasion)- PredictPredict key genetic events by MRI- IdentifyIdentify patients who are candidates for the targeted treatment
Tumor Segmentation. 65 year old male patient with a right temporal GBM. Segmentation of tumor edema (blue), enhancement (yellow) and necrosis (red) was performed and edema volume was obtained.
(1,510 hybridization probes) were analyzed (Affymetrix/Agilent chip technology) in each patient
• Quantitative edema volumes for each patient (N=78) were obtainedHigh and low groups corresponding to volumes of high and low peritumoral edema/invasion were analyzed/compared for differential genomic expression profiles
• Comparative Marker Selection (Broad Institute) Statistical method to identify preferentially upregulated genomic events in one vs. another predefined patient group (high_low)
• Ingenuity Pathway Analysis (IPA) was used to determine gene ontology
Example of a patient with high edema/tumor infiltrationExample of a patient with high edema/tumor infiltration
Our genes and microRNAs were more predictive of patient survival than the current Our genes and microRNAs were more predictive of patient survival than the current subclassification schema used in GBM today.subclassification schema used in GBM today.
• In this presentation, we present the first comprehensive image- genomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM
• We identified MRI as a possible screening tool and imaging surrogate for genes and microRNAs involved in GBM cellular migration and invasion
• Specifically, we identified miR-219 and Periostin as a potential therapeutic target against GBM invasion.