Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Korshunov, A; Jakobiec, FA; Eberhart, CG; Hovestadt, V; Capper, D; Jones, DTW; Sturm, D; Stagner, AM; Edward, DP; Eagle, RC; Proia, AD; Koch, A; Ryzhova, M; Ektova, A; Schüller, U; Zheludkova, O; Lichter, P; von Deimling, A; Pfister, SM; Kool, M

Published Date

  • December 2015

Published In

Volume / Issue

  • 35 / 6

Start / End Page

  • 538 - 544

PubMed ID

  • 26183384

Electronic International Standard Serial Number (EISSN)

  • 1440-1789

Digital Object Identifier (DOI)

  • 10.1111/neup.12227


  • eng

Conference Location

  • Australia