Establishing causal relationships between genetic alterations of human cancers and specific
phenotypes of malignancy remains a challenge. We sequentially introduced mutations into
healthy human melanocytes in up to five genes spanning six commonly disrupted
melanoma pathways, forming nine genetically distinct cellular models of melanoma. We
connected mutant melanocyte genotypes to malignant cell expression programs in vitro and
in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis …