title: Spatiotemporal Evolution of the Primary Glioblastoma Genome.
abstract: Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul 06351, Korea.
authors.forename: Jinkuk
authors.initials: J
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 06351, Korea.
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Yang-Soon
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea.
authors.forename: Yanghee
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Nam
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Byung Sup
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kong
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Ho Jun
authors.initials: HJ
authors.lastname: Seol
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea; Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Yeup
authors.initials: Y
authors.lastname: Yoon
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Jeongwu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: peter_park@harvard.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Korea; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea. Electronic address: nsnam@skku.edu.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics*; D005910:Glioma / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D000077204:Temozolomide