> Details

Ryl, Tatsiana; Afanasyeva, Elena; Hartmann, Till; Schwermer, Melanie; Schneider, Markus; Schröder, Christopher; Wagemanns, Maren; Bister, Arthur; Kanber, Deniz; Steenpass, Laura; Schramm, Kathrin; Jones, Barbara; Jones, David T. W.; Biewald, Eva; Astrahantseff, Kathy; Hanenberg, Helmut; Rahmann, Sven; Lohmann, Dietmar R.; Schramm, Alexander; Ketteler, Petra

A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma
  • Contributor: Ryl, Tatsiana; Afanasyeva, Elena; Hartmann, Till; Schwermer, Melanie; Schneider, Markus; Schröder, Christopher; Wagemanns, Maren; Bister, Arthur; Kanber, Deniz; Steenpass, Laura; Schramm, Kathrin; Jones, Barbara; Jones, David T. W.; Biewald, Eva; Astrahantseff, Kathy; Hanenberg, Helmut; Rahmann, Sven; Lohmann, Dietmar R.; Schramm, Alexander; Ketteler, Petra
  • Published: Springer Science and Business Media LLC, 2024
  • Published in: Communications Biology, 7 (2024) 1
  • Language: English
  • DOI: 10.1038/s42003-024-06596-6
  • ISSN: 2399-3642
  • Origination:
  • Footnote:
  • Description: AbstractRetinoblastoma are childhood eye tumors arising from retinal precursor cells. Two distinct retinoblastoma subtypes with different clinical behavior have been described based on gene expression and methylation profiling. Using consensus clustering of DNA methylation analysis from 61 retinoblastomas, we identify a MYCN-driven cluster of subtype 2 retinoblastomas characterized by DNA hypomethylation and high expression of genes involved in protein synthesis. Subtype 2 retinoblastomas outside the MYCN-driven cluster are characterized by high expression of genes from mesodermal development, including NKX2-5. Knockdown of MYCN expression in retinoblastoma cell models causes growth arrest and reactivates a subtype 1-specific photoreceptor signature. These molecular changes suggest that removing the driving force of MYCN oncogenic activity rescues molecular circuitry driving subtype 1 biology. The MYCN-RB gene signature generated from the cell models better identifies MYCN-driven retinoblastoma than MYCN amplification and can identify cases that may benefit from MYCN-targeted therapy. MYCN drives tumor progression in a molecularly defined retinoblastoma subgroup, and inhibiting MYCN activity could restore a more differentiated and less aggressive tumor biology.
  • Access State: Open Access