PMID- 34698864
OWN - NLM
STAT- MEDLINE
DCOM- 20220509
LR  - 20221028
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 24
IP  - 5
DP  - 2022 May 4
TI  - 12p gain is predominantly observed in non-germinomatous germ cell tumors and 
      identifies an unfavorable subgroup of central nervous system germ cell tumors.
PG  - 834-846
LID - 10.1093/neuonc/noab246 [doi]
AB  - BACKGROUND: Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms 
      predominantly arising in pediatric and young adult populations. While germinomas 
      generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) 
      require more intensive treatment. This study aimed to determine whether 12p gain 
      could predict the prognosis of CNS GCTs. METHODS: Eighty-two CNS GCTs were 
      included in this study. The 12p gain was defined by an additional 12p in the 
      background of potential polyploidy or polysomy. Cases were analyzed using an 
      Illumina methylation 450K array for copy number investigations and validated by 
      fluorescence in situ hybridization (FISH). RESULTS: A 12p gain was found in 
      25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases 
      and 50% of NGGCT cases), particularly in cases with malignant components, such as 
      immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p 
      gain and KIT mutation were mutually exclusive events. The presence of 12p gain 
      correlated with shorter progression-free (PFS) and overall survival (OS) (10-year 
      OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with 
      histology and tumor markers incorporated in the multivariate analysis. Among 
      NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 
      47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among 
      histological components in mixed GCTs. CONCLUSIONS: 12p gain may predict the 
      presence of malignant components of NGGCTs, and poor prognosis of the patients. 
      It may be associated with early tumorigenesis of CNS GCT.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Satomi, Kaishi
AU  - Satomi K
AD  - Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, 
      Japan.
AD  - Division of Brain Tumor Translational Research, National Cancer Center Research 
      Institute, Tokyo, Japan.
FAU - Takami, Hirokazu
AU  - Takami H
AUID- ORCID: 0000-0001-9742-7462
AD  - Division of Brain Tumor Translational Research, National Cancer Center Research 
      Institute, Tokyo, Japan.
AD  - Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, 
      Japan.
FAU - Fukushima, Shintaro
AU  - Fukushima S
AD  - Division of Brain Tumor Translational Research, National Cancer Center Research 
      Institute, Tokyo, Japan.
FAU - Yamashita, Satoshi
AU  - Yamashita S
AD  - Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Matsushita, Yuko
AU  - Matsushita Y
AD  - Division of Brain Tumor Translational Research, National Cancer Center Research 
      Institute, Tokyo, Japan.
FAU - Nakazato, Yoichi
AU  - Nakazato Y
AD  - Department of Pathology, Hidaka Hospital, Gunma, Japan.
FAU - Suzuki, Tomonari
AU  - Suzuki T
AD  - Department of Neuro-Oncology/Neurosurgery, Saitama Medical University 
      International Medical Center, Saitama, Japan.
FAU - Tanaka, Shota
AU  - Tanaka S
AD  - Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, 
      Japan.
FAU - Mukasa, Akitake
AU  - Mukasa A
AD  - Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, 
      Japan.
AD  - Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto 
      University, Kumamoto, Japan.
FAU - Saito, Nobuhito
AU  - Saito N
AD  - Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, 
      Japan.
FAU - Kanamori, Masayuki
AU  - Kanamori M
AD  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, 
      Miyagi, Japan.
FAU - Kumabe, Toshihiro
AU  - Kumabe T
AD  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, 
      Miyagi, Japan.
AD  - Department of Neurosurgery, Kitasato University, Kanagawa, Japan.
FAU - Tominaga, Teiji
AU  - Tominaga T
AD  - Department of Neurosurgery, Tohoku University Graduate School of Medicine, 
      Miyagi, Japan.
FAU - Kobayashi, Keiichi
AU  - Kobayashi K
AD  - Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
FAU - Nagane, Motoo
AU  - Nagane M
AUID- ORCID: 0000-0002-0018-1652
AD  - Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
FAU - Iuchi, Toshihiko
AU  - Iuchi T
AD  - Department of Neurosurgery, Chiba Cancer Center, Chiba, Japan.
FAU - Yoshimoto, Koji
AU  - Yoshimoto K
AD  - Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
AD  - Department of Neurosurgery, Graduate School of Medical and Dental Sciences, 
      Kagoshima University, Kagoshima, Japan.
FAU - Tamura, Kaoru
AU  - Tamura K
AD  - Department of Functional Neurosurgery, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Maehara, Taketoshi
AU  - Maehara T
AD  - Department of Functional Neurosurgery, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Sakai, Keiichi
AU  - Sakai K
AD  - Department of Neurosurgery, Shinshu Ueda Medical Center, Nagano, Japan.
FAU - Sugiyama, Kazuhiko
AU  - Sugiyama K
AD  - Department of Clinical Oncology and Neuro-Oncology Program, Cancer Treatment 
      Center, Hiroshima University Hospital, Hiroshima, Japan.
FAU - Yokogami, Kiyotaka
AU  - Yokogami K
AD  - Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 
      Miyazaki, Japan.
FAU - Takeshima, Hideo
AU  - Takeshima H
AD  - Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, 
      Miyazaki, Japan.
FAU - Nonaka, Masahiro
AU  - Nonaka M
AD  - Department of Neurosurgery, Kansai Medical University Hospital, Osaka, Japan.
FAU - Asai, Akio
AU  - Asai A
AD  - Department of Neurosurgery, Kansai Medical University Hospital, Osaka, Japan.
FAU - Ushijima, Toshikazu
AU  - Ushijima T
AD  - Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
FAU - Matsutani, Masao
AU  - Matsutani M
AD  - Gotanda Rehabilitation Hospital, Tokyo, Japan.
FAU - Nishikawa, Ryo
AU  - Nishikawa R
AD  - Department of Neuro-Oncology/Neurosurgery, Saitama Medical University 
      International Medical Center, Saitama, Japan.
FAU - Ichimura, Koichi
AU  - Ichimura K
AD  - Division of Brain Tumor Translational Research, National Cancer Center Research 
      Institute, Tokyo, Japan.
AD  - Department of Brain Disease Translational Research, Juntendo University Faculty 
      of Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - Nonseminomatous germ cell tumor
SB  - IM
MH  - *Brain Neoplasms/genetics/therapy
MH  - *Central Nervous System Neoplasms/genetics/pathology
MH  - Child
MH  - *Germinoma
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - *Neoplasms, Germ Cell and Embryonal/genetics/therapy
MH  - *Pineal Gland/pathology
MH  - *Testicular Neoplasms
PMC - PMC9071297
OTO - NOTNLM
OT  - 12p gain
OT  - DNA methylation
OT  - FISH
OT  - central nervous system germ cell tumor
OT  - copy number alteration
EDAT- 2021/10/27 06:00
MHDA- 2022/05/10 06:00
PMCR- 2022/10/26
CRDT- 2021/10/26 12:29
PHST- 2021/10/27 06:00 [pubmed]
PHST- 2022/05/10 06:00 [medline]
PHST- 2021/10/26 12:29 [entrez]
PHST- 2022/10/26 00:00 [pmc-release]
AID - 6410684 [pii]
AID - noab246 [pii]
AID - 10.1093/neuonc/noab246 [doi]
PST - ppublish
SO  - Neuro Oncol. 2022 May 4;24(5):834-846. doi: 10.1093/neuonc/noab246.