Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup‐specific prognostic stratification using economical/accessible diagnostic methods

Medulloblastoma (MB) is a biologically and clinically heterogeneous pediatric brain tumor. However, large-scale molecular subgrouping studies have mainly been conducted in Western populations, and comprehensive data from Asia are limited. To address this gap, we analyzed 242 MB cases collected from 39 institutions through the Japan Pediatric Molecular Neuro-Oncology Group, performing centralized molecular classification using NanoString-based gene expression profiling, DNA methylation arrays, and multiplex ligation-dependent probe amplification (MLPA)-based copy number profiling, supplemented by targeted sequencing. The subgroup distribution was 16.1% WNT, 24.8% SHH, 17.4% Group 3, and 41.7% Group 4. CTNNB1 mutations and monosomy 6 characterized all WNT cases, whereas MYCN amplification and TP53 mutations were independent adverse markers in SHH MB. Group 3 showed the worst survival, with MYC amplification and metastasis as poor prognostic factors. In Group 4, large cell/anaplastic histology predicted poor outcomes, whereas chromosome 11 loss was correlated with a favorable prognosis. Whole chromosomal aberration-defined favorable-risk patterns consistently indicate improved outcomes in non-WNT/non-SHH MBs. We also developed a simplified MLPA-based classifier targeting six loci on chromosomes 7, 8, and 11 (SEE-6-CNA), which enabled robust and clinically feasible prognostic stratification. Overall, our findings confirm that the molecular subgroup-specific features of Japanese MBs are largely concordant with global observations and that SEE-6-CNA provides a cost-effective tool to support individualized treatment planning, particularly in resource-limited settings.

Authors

Institutions

Publication Details

Journal
Brain Pathology
Published
2026-03-11
DOI
https://doi.org/10.1111/bpa.70092
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup‐specific prognostic stratification using economical/accessible diagnostic methods

Atsuko Harada, Masahiro Nonaka, Kosuke Nakajo, Yonehiro Kanemura et al.
Brain Pathology
Glioma Diagnosis and Treatment
article

Molecular and clinical features of a Japanese medulloblastoma cohort: Subgroup‐specific prognostic stratification using economical/accessible diagnostic methods

Atsuko Harada, Masahiro Nonaka, Kosuke Nakajo, Yonehiro Kanemura, Yuko Matsushita, Dai Keino, Takeshi Kawauchi, Akira Sasaki, Mizuki Kambara, Junko Hirato, Shigeru Yamaguchi, Yasuhiko Hayashi, Asako Katsuma, Kazuhisa Yoshifuji, Ryuji Ishizaki, Masayoshi Yamaoka, Y. D. Park, Yoshiteru Nakano, Tadashi Suzuki, R. Nishikawa, Daisuke Kanematsu, Masayuki Kanamori, Tadashi Higuchi, Kazuhiko Kurozumi, Keishi Horiguchi, Noriyuki Kijima, Yukihiko Sonoda, Yoshinori Kodama, Soichiro Shibui, Joji Ishida, Takafumi Wataya, Kohei Fukuoka, Motoo Nagane, Kei Tanaka, Noriyoshi Takebe, Yoshitaka Narita, Masazumi Fujii, Masaru Nakada, Atsufumi Kawamura, Kohichi Go, Tomoru Miwa, Kenichi Ishibashi, Koji Adachi, Hideo Nakamura, Yohei Mineharu, Masayuki Mano, Soichi Oya, Yasuhide Makino, Michael D. Taylor, Ryo Ando, Shigeo Ohba, Junya Fukai, Koichi Ichimura, Yosuke Miyairi, Ai Muroi, Tomoko Shofuda, Ryuta Saito, Hiroaki Sakamoto, Ema Yoshioka, Kuniaki Saito, Takuya Akai, Yusuke Kobayashi, Hajime Arai, Daisuke Kuga, Koji Yoshimoto, Takeshi Inoue, Yoshiki Arakawa, Isao Date, Naoki Kagawa, Akitake Mukasa, Kai Yamasaki
article en

Abstract

Medulloblastoma (MB) is a biologically and clinically heterogeneous pediatric brain tumor. However, large-scale molecular subgrouping studies have mainly been conducted in Western populations, and comprehensive data from Asia are limited. To address this gap, we analyzed 242 MB cases collected from 39 institutions through the Japan Pediatric Molecular Neuro-Oncology Group, performing centralized molecular classification using NanoString-based gene expression profiling, DNA methylation arrays, and multiplex ligation-dependent probe amplification (MLPA)-based copy number profiling, supplemented by targeted sequencing. The subgroup distribution was 16.1% WNT, 24.8% SHH, 17.4% Group 3, and 41.7% Group 4. CTNNB1 mutations and monosomy 6 characterized all WNT cases, whereas MYCN amplification and TP53 mutations were independent adverse markers in SHH MB. Group 3 showed the worst survival, with MYC amplification and metastasis as poor prognostic factors. In Group 4, large cell/anaplastic histology predicted poor outcomes, whereas chromosome 11 loss was correlated with a favorable prognosis. Whole chromosomal aberration-defined favorable-risk patterns consistently indicate improved outcomes in non-WNT/non-SHH MBs. We also developed a simplified MLPA-based classifier targeting six loci on chromosomes 7, 8, and 11 (SEE-6-CNA), which enabled robust and clinically feasible prognostic stratification. Overall, our findings confirm that the molecular subgroup-specific features of Japanese MBs are largely concordant with global observations and that SEE-6-CNA provides a cost-effective tool to support individualized treatment planning, particularly in resource-limited settings.

Brain Pathology
Kanazawa University (JP), Hokkaido University of Science (JP), Kurume University (JP), Yamagata University (JP), Jikei University School of Medicine (JP), SHOWA Medical University (JP), Kansai Medical University (JP), Fukushima Medical University (JP), Kyushu University (JP), Fujita Health University (JP), University of Tsukuba (JP), Okayama University (JP), Kanazawa Medical University (JP), Gunma University (JP), Shimane University (JP), Baylor College of Medicine (US), University of Occupational and Environmental Health Japan (JP), Wakayama Medical University (JP), Kyorin University (JP), Tohoku University (JP), Keio University (JP), Hokkaido University (JP), Kyoto University (JP), Hamamatsu University School of Medicine (JP), University of Shimane (JP), Osaka City University (JP), Juntendo University (JP), Osaka National Hospital (JP), Nippon Medical School Musashi Kosugi Hospital (JP), Saitama Children's Medical Center (JP), Teikyo University Hospital (JP), Osaka City General Hospital (JP), National Hospital Organization Hokkaido Medical Center (JP), Nara Medical University Hospital (JP), Kanagawa Children's Medical Center (JP), Kobe Children's Hospital (JP), Yukioka Hospital (JP), Saitama International Medical Center (JP), Chiba Hospital (JP), Nagano Children's Hospital (JP), Tokyo Metropolitan Children's Medical Center (JP), National Cancer Center Hospital East (JP), Texas Children's Hospital (US), Children's Cancer Center (US), Osaka International Cancer Institute (JP), Institute of Applied Biochemistry (JP), Shizuoka Children's Hospital (JP), Kitano Hospital (JP), Takatsuki General Hospital (JP), University of Toyama (JP), Nagoya University (JP), Nara Medical University (JP), Kobe University (JP), Tokyo Metropolitan University (JP), Nippon Medical School (JP), Saitama Medical University (JP), Teikyo University (JP), Kumamoto University (JP), The University of Osaka (JP)
Openalex Percentile: Top 28%
Glioma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.