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11.01.2017 | Original Paper

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas

verfasst von: 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)

Erschienen in: Acta Neuropathologica | Ausgabe 3/2017

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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 non-germinomatous 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 mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide 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 mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

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Titel: Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas
verfasst von: 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)
Publikationsdatum: 11.01.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 3/2017
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1673-2

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Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas

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