title: Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma.
abstract: We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM.
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul, Korea.
authors: Doo-Sik
authors: DS
authors: Kong
authors: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul, Korea.
authors: Jinkuk
authors: J
authors: Kim
authors: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul, Korea.
authors: In-Hee
authors: IH
authors: Lee
authors: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Sung Tae
authors: ST
authors: Kim
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Ho Jun
authors: HJ
authors: Seol
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jung-Il
authors: JI
authors: Lee
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors: Woong-Yang
authors: WY
authors: Park
authors: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Gyuha
authors: G
authors: Ryu
authors: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Zichen
authors: Z
authors: Wang
authors: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Avi
authors: A
authors: Ma'ayan
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea.|Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul, Korea.
authors: Do-Hyun
authors: DH
authors: Nam
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D023281:Genomics / Q000379:methods; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D059467:Transcriptome
keywords: glioblastoma; multicentric; radiogenomic