Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities
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Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities. / Korshunov, Andrey; Jakobiec, Frederick A; Eberhart, Charles G; Hovestadt, Volker; Capper, David; Jones, David T W; Sturm, Dominik; Stagner, Anna M; Edward, Deepak P; Eagle, Ralph C; Proia, Alan D; Koch, Arend; Ryzhova, Marina; Ektova, Anastasia; Schüller, Ulrich; Zheludkova, Olga; Lichter, Peter; Deimling, Andreas; Pfister, Stefan M; Kool, Marcel.
in: NEUROPATHOLOGY, Jahrgang 35, Nr. 6, 12.2015, S. 538-44.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities
AU - Korshunov, Andrey
AU - Jakobiec, Frederick A
AU - Eberhart, Charles G
AU - Hovestadt, Volker
AU - Capper, David
AU - Jones, David T W
AU - Sturm, Dominik
AU - Stagner, Anna M
AU - Edward, Deepak P
AU - Eagle, Ralph C
AU - Proia, Alan D
AU - Koch, Arend
AU - Ryzhova, Marina
AU - Ektova, Anastasia
AU - Schüller, Ulrich
AU - Zheludkova, Olga
AU - Lichter, Peter
AU - Deimling, Andreas
AU - Pfister, Stefan M
AU - Kool, Marcel
N1 - © 2015 Japanese Society of Neuropathology.
PY - 2015/12
Y1 - 2015/12
N2 - Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR.
AB - Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR.
KW - Adolescent
KW - Adult
KW - Central Nervous System Neoplasms
KW - Child
KW - Child, Preschool
KW - Cluster Analysis
KW - Eye Neoplasms
KW - Female
KW - Gene Dosage
KW - Humans
KW - Infant
KW - Male
KW - Middle Aged
KW - Neoplasms, Germ Cell and Embryonal
KW - Neuroectodermal Tumors, Primitive
KW - Oligonucleotide Array Sequence Analysis
KW - Retrospective Studies
KW - Transcriptome
KW - Comparative Study
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1111/neup.12227
DO - 10.1111/neup.12227
M3 - SCORING: Journal article
C2 - 26183384
VL - 35
SP - 538
EP - 544
JO - NEUROPATHOLOGY
JF - NEUROPATHOLOGY
SN - 0919-6544
IS - 6
ER -
