title: Spatiotemporal genomic architecture informs precision oncology in glioblastoma.
abstract: Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies. However, this proposition is complicated by spatial and temporal heterogeneity. Here we study genomic and expression profiles across 127 multisector or longitudinal specimens from 52 individuals with glioblastoma (GBM). Using bulk and single-cell data, we find that samples from the same tumor mass share genomic and expression signatures, whereas geographically separated, multifocal tumors and/or long-term recurrent tumors are seeded from different clones. Chemical screening of patient-derived glioma cells (PDCs) shows that therapeutic response is associated with genetic similarity, and multifocal tumors that are enriched with PIK3CA mutations have a heterogeneous drug-response pattern. We show that targeting truncal events is more efficacious than targeting private events in reducing the tumor burden. In summary, this work demonstrates that evolutionary inference from integrated genomic analysis in multisector biopsies can inform targeted therapeutic interventions for patients with GBM.
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jin-Ku
authors.identifier: http://orcid.org/0000-0003-0263-3234
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.|Divisions of Life Science and Biomedical Engineering, Hong Kong University of Science and Technology, Hong Kong.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Sa
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Ladewig
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hae-Ock
authors.initials: HO
authors.lastname: Lee
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Daniel S
authors.identifier: http://orcid.org/0000-0003-1413-3907
authors.initials: DS
authors.lastname: Rosenbloom
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Camara
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: van Nieuwenhuizen
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Sang Won
authors.identifier: http://orcid.org/0000-0003-3073-4411
authors.initials: SW
authors.lastname: Jung
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Junhyung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chen
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Sang
authors.initials: S
authors.lastname: Shin
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yun Jee
authors.initials: YJ
authors.lastname: Seo
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jin-Mi
authors.initials: JM
authors.lastname: Oh
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yong Jae
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Department of Neurosurgery, College of Medicine, Seoul National University and Seoul National University Hospital, Seoul, Republic of 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, Republic of 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, Republic of Korea.
authors.forename: Ho Jun
authors.initials: HJ
authors.lastname: Seol
authors.affiliation: Department of Mathematics, University of Texas, Austin, Texas, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Blumberg
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, New York, USA.|Department of Neurology, Columbia University, New York, New York, USA.|Department of Pathology, Columbia University, New York, New York, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iavarone
authors.affiliation: Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.|Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Woong-Yang
authors.identifier: http://orcid.org/0000-0003-4234-0380
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Systems Biology, Columbia University, New York, New York, USA.|Department of Biomedical Informatics, Columbia University, New York, New York, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D023281:Genomics / Q000379:methods; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D057285:Precision Medicine / Q000379:methods
chemical_list: D019869:Phosphatidylinositol 3-Kinases