ABSTRACT: Drug resistant population of PC9(human non-small cell lung cancer) or A375 (human melanoma) cell lines were used for this study. By exome sequencing, we will analyse mutations of cells in drug tolerent state and after drug holiday.
Project description:Drug resistant population of PC9(human non-small cell lung cancer) or A375 (human melanoma) cell lines were used for this study. By exome sequencing, we will analyse mutations of cells in drug tolerent state and after drug holiday. .
This dataset contains all the data available for this study on 2019-04-03.
Project description:BRAF targeted drug vemurafenib have shown very good clinical benefit in melanoma patient containing BRAF V600E mutation. However, resistance always occurs in patient. Early stage of the resistance development require the tumor cell adapted to the targeted drug. We are trying to study the kinetic of melanoma cell adaptation towards vemurafenib. 10 melanoma cell lines with BRAF mutation are treated with targeted therapy vemurafenib. RNA-seq samples are collected after drug treatment for different time (day3 and day21) to compare with DMSO-treated control samples for each cell line. Except innate resistant cell line M381, all other cell lines shows inhibition of proliferation. However, a small cluster of cell lines (M397, M229 and M263) shows some other unique transcriptomic change. For cell line M397, M229 and M263, we also collected the RNA-seq data for long-term (73day/90day) drug treatment condition where the cells developed resistance to vemurafenib treatment. Dedifferentiation is enriched in these unique transcriptomic change within these 3 cell lines. Similar cell state dedifferentiation phenomenon is also reported to cause resistance towards immunotherpay where the resistant de-differentiated melanoma cells are induced by TNF which is secreted by tumor-infiltrating T cells. We also treat our cultured melanoma cells with TNF and collected the treated sample for RNA-seq experiment.
Project description:aCGH of human melanoma cell lines comparing parental (drug sensitve) vs isogenic drug resistant-derived subline Two condition experiment: two BRAF-V600E mutant cell lines (drug sensitive - parental baseline) vs two derived sublines after chronic exposure to the MEK inhibitor trametinib (drug resistant) are compared
Project description:We generated four drug-resistant melanoma cell lines from paired primary/metastatic cell lines using PLX4720 and used for Affymetrix Human Gene 1.0 ST array
Project description:Melanoma cell lines were assessed for differences in gene expression patterns between the lines sensitive and resistant to BRAF and MEK inhibitor drugs. 22 BRAF-mutant melanoma cell lines were assessed for response to BRAF and MEK inhibitors in a 3 day drug treatment dose response assay. Based on the IC50, 18 lines were found to be responsive to BRAF or MEK inhibition and 4 were resistant. Normalised gene expression data generated from experimental replicate affymetrix arrays was assessed to identify differential patterns of inherent gene expression between the cell lines grouped as drug-responsive or drug-resistant. This were used to idenify specific candidate genes and pathways associated with inherent BRAF/MEK inhibitor drug resistance in melanoma cells.
Project description:In vitro cell cultures are frequently used to define the molecular background of drug resistance. In this study our major aim was to compare the gene expression signature of 2D and 3D cultured BRAFV600E mutant melanoma cell lines. We successfully developed BRAF-drug resistant cell lines from paired primary/metastatic melanoma cell lines in both 2D and 3D in vitro cultures. Using Affymetrix Human Gene 1.0 ST arrays, we determined the gene expression pattern of all cell lines. Our study highlights gene expression alterations that might help to understand the development of acquired resistance in melanoma cells in tumour tissue.
Project description:Whole-exome sequencing was performed on DNA samples extracted from seven melanoma cell lines resistant to either vemurafenib (BRAF V600E inhibitor) or trametinib (MEK1/2 inhibitor). The aim of the experiment was to search for genetic alterations responsible for phenotypic diversity of melanoma cell lines reported at the level of cell morphology, activity of signaling pathways essential for melanoma development and progression, and resistance to targeted therapeutics.
Project description:Whole-exome sequencing was performed on DNA samples extracted from seven melanoma cell lines resistant to either vemurafenib (BRAF V600E inhibitor) or trametinib (MEK1/2 inhibitor). The aim of the experiment was to search for genetic alterations responsible for phenotypic diversity of melanoma cell lines reported at the level of cell morphology, activity of signaling pathways essential for melanoma development and progression, and resistance to targeted therapeutics.
