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@ARTICLE{Ryl:291942,
author = {T. Ryl and E. Afanasyeva and T. Hartmann and M. Schwermer
and M. Schneider and C. Schröder and M. Wagemanns and A.
Bister and D. Kanber and L. Steenpass and K. Schramm$^*$ and
B. Jones$^*$ and D. Jones$^*$ and E. Biewald and K.
Astrahantseff and H. Hannenberg and S. Rahmann and D. R.
Lohmann and A. Schramm and P. Ketteler},
title = {{A} {MYCN}-driven de-differentiation profile identifies a
subgroup of aggressive retinoblastoma.},
journal = {Communications biology},
volume = {7},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2024-01550},
pages = {919},
year = {2024},
abstract = {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.},
keywords = {Humans / Retinoblastoma: genetics / Retinoblastoma:
pathology / N-Myc Proto-Oncogene Protein: genetics / N-Myc
Proto-Oncogene Protein: metabolism / DNA Methylation /
Retinal Neoplasms: genetics / Retinal Neoplasms: pathology /
Retinal Neoplasms: metabolism / Gene Expression Regulation,
Neoplastic / Cell Line, Tumor / Cell Dedifferentiation:
genetics / Female / Male / Child, Preschool / N-Myc
Proto-Oncogene Protein (NLM Chemicals) / MYCN protein, human
(NLM Chemicals)},
cin = {B360},
ddc = {570},
cid = {I:(DE-He78)B360-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39079981},
doi = {10.1038/s42003-024-06596-6},
url = {https://inrepo02.dkfz.de/record/291942},
}