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000291942 1001_ $$aRyl, Tatsiana$$b0
000291942 245__ $$aA MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma.
000291942 260__ $$aLondon$$bSpringer Nature$$c2024
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000291942 520__ $$aRetinoblastoma are childhood eye tumors arising from retinal precursor cells. Two distinct retinoblastoma subtypes with different clinical behavior have been described based on gene expression and methylation profiling. Using consensus clustering of DNA methylation analysis from 61 retinoblastomas, we identify a MYCN-driven cluster of subtype 2 retinoblastomas characterized by DNA hypomethylation and high expression of genes involved in protein synthesis. Subtype 2 retinoblastomas outside the MYCN-driven cluster are characterized by high expression of genes from mesodermal development, including NKX2-5. Knockdown of MYCN expression in retinoblastoma cell models causes growth arrest and reactivates a subtype 1-specific photoreceptor signature. These molecular changes suggest that removing the driving force of MYCN oncogenic activity rescues molecular circuitry driving subtype 1 biology. The MYCN-RB gene signature generated from the cell models better identifies MYCN-driven retinoblastoma than MYCN amplification and can identify cases that may benefit from MYCN-targeted therapy. MYCN drives tumor progression in a molecularly defined retinoblastoma subgroup, and inhibiting MYCN activity could restore a more differentiated and less aggressive tumor biology.
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000291942 650_7 $$2NLM Chemicals$$aN-Myc Proto-Oncogene Protein
000291942 650_7 $$2NLM Chemicals$$aMYCN protein, human
000291942 650_2 $$2MeSH$$aHumans
000291942 650_2 $$2MeSH$$aRetinoblastoma: genetics
000291942 650_2 $$2MeSH$$aRetinoblastoma: pathology
000291942 650_2 $$2MeSH$$aN-Myc Proto-Oncogene Protein: genetics
000291942 650_2 $$2MeSH$$aN-Myc Proto-Oncogene Protein: metabolism
000291942 650_2 $$2MeSH$$aDNA Methylation
000291942 650_2 $$2MeSH$$aRetinal Neoplasms: genetics
000291942 650_2 $$2MeSH$$aRetinal Neoplasms: pathology
000291942 650_2 $$2MeSH$$aRetinal Neoplasms: metabolism
000291942 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000291942 650_2 $$2MeSH$$aCell Line, Tumor
000291942 650_2 $$2MeSH$$aCell Dedifferentiation: genetics
000291942 650_2 $$2MeSH$$aFemale
000291942 650_2 $$2MeSH$$aMale
000291942 650_2 $$2MeSH$$aChild, Preschool
000291942 7001_ $$aAfanasyeva, Elena$$b1
000291942 7001_ $$00000-0002-6993-347X$$aHartmann, Till$$b2
000291942 7001_ $$aSchwermer, Melanie$$b3
000291942 7001_ $$00000-0001-6634-4306$$aSchneider, Markus$$b4
000291942 7001_ $$aSchröder, Christopher$$b5
000291942 7001_ $$aWagemanns, Maren$$b6
000291942 7001_ $$aBister, Arthur$$b7
000291942 7001_ $$aKanber, Deniz$$b8
000291942 7001_ $$aSteenpass, Laura$$b9
000291942 7001_ $$0P:(DE-He78)2f592d9d8339bee07cca3956b7472b61$$aSchramm, Kathrin$$b10$$udkfz
000291942 7001_ $$0P:(DE-He78)fae1bf941c5fd76cf5356ecfa1243cc4$$aJones, Barbara$$b11$$udkfz
000291942 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b12$$udkfz
000291942 7001_ $$aBiewald, Eva$$b13
000291942 7001_ $$00000-0002-7872-1997$$aAstrahantseff, Kathy$$b14
000291942 7001_ $$aHannenberg, Helmut$$b15
000291942 7001_ $$aRahmann, Sven$$b16
000291942 7001_ $$aLohmann, Dietmar R$$b17
000291942 7001_ $$00000-0001-7670-7529$$aSchramm, Alexander$$b18
000291942 7001_ $$00000-0002-8138-0441$$aKetteler, Petra$$b19
000291942 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-024-06596-6$$gVol. 7, no. 1, p. 919$$n1$$p919$$tCommunications biology$$v7$$x2399-3642$$y2024
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