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Developmental chromatin programs determine oncogenic competence in melanoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Danio rerio Homo sapiens

PROVIDER: GSE172069 | GEO | 2021/04/15

REPOSITORIES: GEO

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Developmental chromatin programs determine oncogenic competence in melanoma.

Project description:Oncogenes only transform cells under certain cellular contexts, a phenomenon called oncogenic competence. Using a combination of a human pluripotent stem cell–derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600E along with additional mutations depends on the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are less responsive to mutations, whereas both neural crest and melanoblast populations are readily transformed. Profiling reveals that progenitors have higher expression of chromatin-modifying enzymes such as ATAD2, a melanoma competence factor that forms a complex with SOX10 and allows for expression of downstream oncogenic and neural crest programs. These data suggest that oncogenic competence is mediated by regulation of developmental chromatin factors, which then allow for proper response to those oncogenes.

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Developmental chromatin programs determine oncogenic competence in melanoma [Zebrafish]

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Developmental chromatin programs determine oncogenic competence in melanoma [Cut&Run]

Project description:We perfomed Cut&Run for ATAD2, MYC and SOX10 in 3xKO ATAD2 dox melanocytes and 3xKO dox melanocytes. We used 10'000 cells per condition and the protocol was performed as in Skene et al., 2018. We could show that, in the 3xKO ATAD2 dox melanocytes, ATAD2, MYC and SOX10 have common targets. Many of those targets belong to a developmental signature typical of the neural crest and to the MAPK pathway.

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Developmental chromatin programs determine oncogenic competence in melanoma

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