(A) Determination of differentiation states of skin cutaneous melanoma (SKCM) biopsies from the TCGA cohort (n=458) The vast majority of these tumors exhibited a differentiated profile (89%; melanocytic and transitory states). The others display a dedifferentiated profile (11%; neural crest-like cells and undifferentiated states). Human melanoma 501Mel cell line is classified as differentiated melanoma cells (melanocytic cells), according to the gene expression profile (four categories were defined by (Tsoi et al, 2018); melanocytic, transitory, neural crest-like and undifferentiated cells). 501mel cell line was selected for the CRISPR screens. 