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Cancer Cell. 2015 Sep 14;28(3):318-28. doi: 10.1016/j.ccell.2015.07.013.

Spatiotemporal Evolution of the Primary Glioblastoma Genome.

Author information

1
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul 06351, Korea.
2
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
3
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.
4
Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 06351, Korea.
5
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
6
Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, Korea.
7
Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
8
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.
9
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.
10
Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
11
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.
12
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.

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.

PMID:
26373279
DOI:
10.1016/j.ccell.2015.07.013
[Indexed for MEDLINE]
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