Journal: iScience

Article Title: Understanding cancer drug resistance with Sleeping Beauty functional genomic screens: Application to MAPK inhibition in cutaneous melanoma

doi: 10.1016/j.isci.2023.107805

Figure Lengend Snippet: Sleeping Beauty genetic screen strategy and melanoma BRAF/MEK inhibition screen results (A) Schematic of the genetic screens. (B) Circos plot of insertion sites in unselected samples (left) and BRAF/MEKi selected samples (right). Each ring displays data from the screen for a given cell line. (C) Boxplots showing the number of unique genes mutated per 10cm plate for a given cell line screen. The right Y axis is for UACC257 data. The edges of the boxes denote the 1st and 3rd quartiles, and the line denotes the 2nd quartile. (D) Line plot showing the number of true positive drivers detected when using a subset of n samples. The X axis denotes n. True positive drivers are those that passed filtering when using the entire dataset. The error bars denote the 95% confidence interval. (E) Heatmap of the -log(q-value) for select candidates recovered in our genetic screens. The q value is the multi-hypothesis corrected p value generated by performing a chi-squared test based on the observed number of insertions in a gene and the expected number of insertions in a gene. The expected number of insertions is derived from the number of TA sites in a gene and the total number of insertions in the dataset.

Article Snippet: We performed cell-based SB mutagenesis in five BRAF V600 E/K melanoma cell lines against encorafenib (ENCOR) and binitmetinib, which are inhibitors of BRAF and MEK, respectively., , , , , , , Compared to VEM, ENCOR binds more strongly to BRAF V600 E/K , which translated to improved overall survival compared to VEM in a clinical trial.

Techniques: Inhibition, Generated, Derivative Assay

Journal: iScience

Article Title: Understanding cancer drug resistance with Sleeping Beauty functional genomic screens: Application to MAPK inhibition in cutaneous melanoma

doi: 10.1016/j.isci.2023.107805

Figure Lengend Snippet:

Article Snippet: We performed cell-based SB mutagenesis in five BRAF V600 E/K melanoma cell lines against encorafenib (ENCOR) and binitmetinib, which are inhibitors of BRAF and MEK, respectively., , , , , , , Compared to VEM, ENCOR binds more strongly to BRAF V600 E/K , which translated to improved overall survival compared to VEM in a clinical trial.

Techniques: Recombinant, Reverse Transcription, Transfection, RNA Extraction, Plasmid Preparation, Software