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

On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium)

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)445-462
Number of pages18
JournalActa Neuropathologica
Volume133
Issue number3
DOIs
Publication statusPublished - 01-03-2017

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Germinoma
Germ Cell and Embryonal Neoplasms
Germ Cells
Methylation
Genome
DNA Methylation
Phosphatidylinositol 3-Kinases
Retroelements
Mutation
DNA Fingerprinting
Epigenomics
Brain Neoplasms
Cell Movement
Japan
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium). / Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. In: Acta Neuropathologica. 2017 ; Vol. 133, No. 3. pp. 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 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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On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium) 2017, 'Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas', Acta Neuropathologica, vol. 133, no. 3, pp. 445-462. https://doi.org/10.1007/s00401-017-1673-2

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. / On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium).

In: Acta Neuropathologica, Vol. 133, No. 3, 01.03.2017, p. 445-462.

Research output: Contribution to journalArticle

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AU - Yamashita, Satoshi

AU - Kobayashi, Hisato

AU - Takami, Hirokazu

AU - Fukuoka, Kohei

AU - Nakamura, Taishi

AU - Yamasaki, Kai

AU - Matsushita, Yuko

AU - Nakamura, Hiromi

AU - Totoki, Yasushi

AU - Kato, Mamoru

AU - Suzuki, Tomonari

AU - Mishima, Kazuhiko

AU - Yanagisawa, Takaaki

AU - Mukasa, Akitake

AU - Saito, Nobuhito

AU - Kanamori, Masayuki

AU - Kumabe, Toshihiro

AU - Tominaga, Teiji

AU - Nagane, Motoo

AU - Iuchi, Toshihiko

AU - Yoshimoto, Koji

AU - Mizoguchi, Masahiro

AU - Tamura, Kaoru

AU - Sakai, Keiichi

AU - Sugiyama, Kazuhiko

AU - Nakada, Mitsutoshi

AU - Yokogami, Kiyotaka

AU - Takeshima, Hideo

AU - Kanemura, Yonehiro

AU - Matsuda, Masahide

AU - Matsumura, Akira

AU - Kurozumi, Kazuhiko

AU - Ueki, Keisuke

AU - Nonaka, Masahiro

AU - Asai, Akio

AU - Kawahara, Nobutaka

AU - Hirose, Yuichi

AU - Takayama, Tatusya

AU - Nakazato, Yoichi

AU - Narita, Yoshitaka

AU - Shibata, Tatsuhiro

AU - Matsutani, Masao

AU - Ushijima, Toshikazu

AU - Nishikawa, Ryo

AU - Ichimura, Koichi

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On behalf of The Intracranial Germ Cell Tumor Genome Analysis Consortium (The iGCTConsortium). Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathologica. 2017 Mar 1;133(3):445-462. https://doi.org/10.1007/s00401-017-1673-2