Journal
CELL REPORTS
Volume 21, Issue 7, Pages 1936-1952Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.10.052
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Funding
- NIH [P01 CA114046, P01 CA025874, R01 CA047159]
- SPORE on Skin Cancer [P50 CA174523]
- Melanoma Research Alliance
- University of Pennsylvania
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
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Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified. Multiple minor melanoma subtypes were also recapitulated, including melanomas with multiple activating mutations in the MAPK-signaling pathway and chromatin-remodeling gene mutations. These well-characterized melanoma PDXs and cell lines can be used not only as reagents for a large array of biological studies but also as pre-clinical models to facilitate drug development.
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