title: Detection of a Distinctive Genomic Signature in Rhabdoid Glioblastoma, A Rare Disease Entity Identified by Whole Exome Sequencing and Whole Transcriptome Sequencing.
abstract: We analyzed the genome of a rhabdoid glioblastoma (R-GBM) tumor, a very rare variant of GBM. A surgical specimen of R-GBM from a 20-year-old woman was analyzed using whole exome sequencing (WES), whole transcriptome sequencing (WTS), single nucleotide polymorphism array, and array comparative genomic hybridization. The status of gene expression in R-GBM tissue was compared with that of normal brain tissue and conventional GBM tumor tissue. We identified 23 somatic non-synonymous small nucleotide variants with WES. We identified the BRAF V600E mutation and possible functional changes in the mutated genes, ISL1 and NDRG2. Copy number alteration analysis revealed gains of chromosomes 3, 7, and 9. We found loss of heterozygosity and focal homozygous deletion on 9q21, which includes CDKN2A and CDKN2B. In addition, WTS revealed that CDK6, MET, EZH2, EGFR, and NOTCH1, which are located on chromosomes 7 and 9, were over-expressed, whereas CDKN2A/2B were minimally expressed. Fusion gene analysis showed 14 candidate genes that may be functionally involved in R-GBM, including TWIST2, and UPK3BL. The BRAF V600E mutation, CDKN2A/2B deletion, and EGFR/MET copy number gain were observed. These simultaneous alterations are very rarely found in GBM. Moreover, the NDRG2 mutation was first identified in this study as it has never been reported in GBM. We observed a unique genomic signature in R-GBM compared to conventional GBM, which may provide insight regarding R-GBM as a distinct disease entity among the larger group of GBMs.
authors: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-799, Korea.
authors: Youngil
authors: Y
authors: Koh
authors: Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, East Campus, Samsung SDS Tower, 123 Olympic Ro 35 Gil, Songpa-gu, Seoul 138-240, Korea.
authors: Inho
authors: I
authors: Park
authors: Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, East Campus, Samsung SDS Tower, 123 Olympic Ro 35 Gil, Songpa-gu, Seoul 138-240, Korea.
authors: Chung-Hyun
authors: CH
authors: Sun
authors: Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, East Campus, Samsung SDS Tower, 123 Olympic Ro 35 Gil, Songpa-gu, Seoul 138-240, Korea.
authors: Seungmook
authors: S
authors: Lee
authors: Bioinformatics Group, Platform Development Center, CSP R&D, Samsung SDS, East Campus, Samsung SDS Tower, 123 Olympic Ro 35 Gil, Songpa-gu, Seoul 138-240, Korea. Electronic address: hongseok.yun@samsung.com.
authors: Hongseok
authors: H
authors: Yun
authors: Department of Neurosurgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-799, Korea.
authors: Chul-Kee
authors: CK
authors: Park
authors: Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-799, Korea; Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Sung-Hye
authors: SH
authors: Park
authors: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Joo Kyung
authors: JK
authors: Park
authors: Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea; Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Electronic address: shlee119@snu.ac.kr.
authors: Se-Hoon
authors: SH
authors: Lee