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MEK inhibition profoundly reprograms myogenic super enhancers in mutant-RAS driven Rhabdomyosarcoma

ABSTRACT: Trametinib-treated rhabdomyosarcoma cells undergo transcriptional reprogramming akin to myogenic differentiation. This reprogramming is induced by loss of ERK-mediated inhibition of MYOG expression. Restoration of MYOG allows establishment of super-enhancers at genes expressed by terminally differentiated myotubes. Our findings demonstrate that aberrant MAP kinase activity blocks differentiation in rhabdomyosarcoma and highlight trametinib as a potential therapeutic for RAS-mutated rhabdomyosarcoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85169 | GEO | 2018/04/01

REPOSITORIES: GEO

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MEK inhibition rewires enhancer landscapes in RAS-driven Rhabdomyosarcoma to unlock a myogenic differentation block

Project description:Trametinib-treated rhabdomyosarcoma cells undergo transcriptional reprogramming akin to myogenic differentiation. This reprogramming is induced by loss of ERK-mediated inhibition of MYOG expression. Restoration of MYOG allows establishment of super-enhancers at genes expressed by terminally differentiated myotubes. Our findings demonstrate that aberrant MAP kinase activity blocks differentiation in rhabdomyosarcoma and highlight trametinib as a potential therapeutic for RAS-mutated rhabdomyosarcoma.

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