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Gene expression profiling of melanoma cell lines with acquired resistance to the BRAF inhibitor PLX4032 and the parental sensitive counterparts and of melanoma cell lines intrinsically resistant.

ABSTRACT: Gene expression profiling of melanoma cell lines with acquired resistance to the BRAF inhibitor PLX4032 and the parental sensitive counterparts and of melanoma cell lines intrinsically resistant.

PROVIDER: PRJNA833454 | ENA |

REPOSITORIES: ENA

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Gene expression profiling of melanoma cell lines with acquired resistance to the BRAF inhibitor PLX4032 and the parental sensitive counterparts and of melanoma cell lines intrinsically resistant.

Project description:Targeted therapy with small molecules inhibiting BRAF and MEK kinase represents a therapeutic option in advanced metastatic melanoma although drug resistance limits the achievement of persistent cures. The genomic analyses of tumors from patients developing treatment resistance indicate that drug tolerance may result from non-mutational events occurring in the tumor microenvironment. To identify tumor specific transcriptional changes related to resistance to the BRAF-inhibitor PLX4032, cell lines with acquired resistance to PLX4032 were generated from six sensitive melanoma lines by chronic in vitro drug exposure (Vergani E, Oncotarget 2016) and analyzed for gene expression profiles; in addition a set of cell lines with intrinsic resistance was included for comparison. Cell lines were obtained from metastatic surgical specimens and were previously genetically characterized (Daniotti M, Oncogene 2004; Vergani E, JID 2022, accepted).

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Expression data from melanoma cell lines

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Project description:We have collected material from a patient who had BrafV600E mutant melanoma that was treated with PLX4032. We have germline DNA from the patient and DNA and RNA from distinct lesions before and after treatment with PLX4032. We have transcriptome sequenced these samples to obtain a snap shot of the mechanisms of resistance that are operative.

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Epigenome analysis of Control and PLX4032 Resistant Clones with EPIC array.

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