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

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.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Fukushima S,Yamashita S,Kobayashi H,Takami H,Fukuoka K,Nakamura T,Yamasaki K,Matsushita Y,Nakamura H,Totoki Y,Kato M,Suzuki T,Mishima K,Yanagisawa T,Mukasa A,Saito N,Kanamori M,Kumabe T,Tominaga T,Nagane M,Iuchi T

doi

10.1007/s00401-017-1673-2

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

445-462

issue

3

eissn

0001-6322

issn

1432-0533

pii

10.1007/s00401-017-1673-2

journal_volume

133

pub_type

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