Nakano Yoshiteru
   Department   School of Medicine  Neurosurgery, Clinical Medical Sciences
   Position  
Article types journal article
Language English
Peer review Peer reviewed
Title Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors.
Journal Formal name:Acta neuropathologica communications
Abbreviation:Acta Neuropathol Commun
ISSN code:20515960/20515960
Volume, Issue, Page 6(1),134頁
Author and coauthor Fukuoka Kohei, Kanemura Yonehiro, Shofuda Tomoko, Fukushima Shintaro, Yamashita Satoshi, Narushima Daichi, Kato Mamoru, Honda-Kitahara Mai, Ichikawa Hitoshi, Kohno Takashi, Sasaki Atsushi, Hirato Junko, Hirose Takanori, Komori Takashi, Satomi Kaishi, Yoshida Akihiko, Yamasaki Kai, Nakano Yoshiko, Takada Ai, Nakamura Taishi, Takami Hirokazu, Matsushita Yuko, Suzuki Tomonari, Nakamura Hideo, Makino Keishi, Sonoda Yukihiko, Saito Ryuta, Tominaga Teiji, Matsusaka Yasuhiro, Kobayashi Keiichi, Nagane Motoo, Furuta Takuya, Nakada Mitsutoshi, Narita Yoshitaka, Hirose Yuichi, Ohba Shigeo, Wada Akira, Shimizu Katsuyoshi, Kurozumi Kazuhiko, Date Isao, Fukai Junya, Miyairi Yousuke, Kagawa Naoki, Kawamura Atsufumi, Yoshida Makiko, Nishida Namiko, Wataya Takafumi, Yamaoka Masayoshi, Tsuyuguchi Naohiro, Uda Takehiro, Takahashi Mayu, Nakano Yoshiteru, Akai Takuya, Izumoto Shuichi, Nonaka Masahiro, Yoshifuji Kazuhisa, Kodama Yoshinori, Mano Masayuki, Ozawa Tatsuya, Ramaswamy Vijay, Taylor Michael D, Us
Publication date 2018/12
Summary Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to f
DOI 10.1186/s40478-018-0630-1
PMID 30514397