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Title of Journal: Acta Neuropathol

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Abbravation: Acta Neuropathologica

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Springer Berlin Heidelberg

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10.1007/bf02674913

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1432-0533

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Genomewide methylation profiles in primary intrac

Authors: Shintaro Fukushima Satoshi Yamashita Hisato Kobayashi Hirokazu Takami Kohei Fukuoka Taishi Nakamura Kai Yamasaki Yuko Matsushita Hiromi Nakamura Yasushi Totoki Mamoru Kato Tomonari Suzuki Kazuhiko Mishima Takaaki Yanagisawa Akitake Mukasa Nobuhito Saito Masayuki Kanamori Toshihiro Kumabe Teiji Tominaga Motoo Nagane Toshihiko Iuchi Koji Yoshimoto Masahiro Mizoguchi Kaoru Tamura Keiichi Sakai Kazuhiko Sugiyama Mitsutoshi Nakada Kiyotaka Yokogami Hideo Takeshima Yonehiro Kanemura Masahide Matsuda Akira Matsumura Kazuhiko Kurozumi Keisuke Ueki Masahiro Nonaka Akio Asai Nobutaka Kawahara Yuichi Hirose Tatusya Takayama Yoichi Nakazato Yoshitaka Narita Tatsuhiro Shibata Masao Matsutani Toshikazu Ushijima Ryo Nishikawa Koichi Ichimura On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium The iGCTConsortium
Publish Date: 2017/01/11
Volume: 133, Issue: 3, Pages: 445-462
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Abstract

Intracranial germ cell tumors iGCTs are the second most common brain tumors among children under 14 in Japan The World Health Organization classification recognizes several subtypes of iGCTs which are conventionally subclassified into pure germinoma or nongerminomatous GCTs Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs however the mechanisms of how different subtypes develop often as a mixedGCT are unknown To elucidate the pathogenesis of iGCTs we investigated 61 GCTs of various subtypes by genomewide DNA methylation profiling We showed that pure germinomas are characterized by global low DNA methylation a unique epigenetic feature making them distinct from all other iGCTs subtypes The patterns of methylation strongly resemble that of primordial germ cells PGC at the migration phase possibly indicating the cell of origin for these tumors Unlike PGC however hypomethylation extends to long interspersed nuclear element retrotransposons Histologically and epigenetically distinct microdissected components of mixedGCTs shared identical somatic mutations in the MAPK or PI3K pathways indicating that they developed from a common ancestral cellWe thank all the participating institutions of the iGCT Genome Analysis Consortium for their valuable support and contributions This work was carried out as a research program of ‘The Project for Development of Innovative Research on Cancer Therapeutics’ PDirect Ministry of Education Culture Sports Science and Technology MEXT of Japan No 15cm0106066h0005 and supported by GrantinAid for Young Scientists B KAKENHI No 30529459 from the Japan Society for the Promotion of Science JSPS Data analysis was supported by National Cancer Center Research and Development Funds 26A5 NCCRI HN YT MK and TS SF is an awardee of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research in Japan for the 3rd Term Comprehensive 10year Strategy for Cancer Control This work is dedicated to the memory of Prof Nobutaka Kawahara

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