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001     291942
005     20250509115332.0
024 7 _ |a 10.1038/s42003-024-06596-6
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082 _ _ |a 570
100 1 _ |a Ryl, Tatsiana
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245 _ _ |a A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma.
260 _ _ |a London
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|b Springer Nature
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520 _ _ |a Retinoblastoma 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.
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650 _ 7 |a N-Myc Proto-Oncogene Protein
|2 NLM Chemicals
650 _ 7 |a MYCN protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Retinoblastoma: genetics
|2 MeSH
650 _ 2 |a Retinoblastoma: pathology
|2 MeSH
650 _ 2 |a N-Myc Proto-Oncogene Protein: genetics
|2 MeSH
650 _ 2 |a N-Myc Proto-Oncogene Protein: metabolism
|2 MeSH
650 _ 2 |a DNA Methylation
|2 MeSH
650 _ 2 |a Retinal Neoplasms: genetics
|2 MeSH
650 _ 2 |a Retinal Neoplasms: pathology
|2 MeSH
650 _ 2 |a Retinal Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Cell Dedifferentiation: genetics
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Child, Preschool
|2 MeSH
700 1 _ |a Afanasyeva, Elena
|b 1
700 1 _ |a Hartmann, Till
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700 1 _ |a Schwermer, Melanie
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700 1 _ |a Schneider, Markus
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700 1 _ |a Schröder, Christopher
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700 1 _ |a Wagemanns, Maren
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700 1 _ |a Bister, Arthur
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700 1 _ |a Kanber, Deniz
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700 1 _ |a Steenpass, Laura
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700 1 _ |a Schramm, Kathrin
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700 1 _ |a Jones, Barbara
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700 1 _ |a Jones, David
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700 1 _ |a Biewald, Eva
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700 1 _ |a Astrahantseff, Kathy
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700 1 _ |a Hannenberg, Helmut
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700 1 _ |a Rahmann, Sven
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700 1 _ |a Lohmann, Dietmar R
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700 1 _ |a Schramm, Alexander
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700 1 _ |a Ketteler, Petra
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773 _ _ |a 10.1038/s42003-024-06596-6
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