4 years ago

Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines

Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines
Giorgos Karakousis, Ioannis N. Anastopoulos, Xaiowei Xu, Wei Xu, Melissa A. Wilson, Bradley Garman, David Elder, Katherine L. Nathanson, Michael A. Davies, Nicholas J. Petrelli, Ravi Amaravadi, Lynn Schuchter, Marilda Beqiri, Tara C. Gangadhar, Xiangfan Yin, Batool Shannan, Nandita Mitra, Dennie T. Frederick, Katrin Sproesser, Michael Guarino, Joseph Bennett, Jennifer Wargo, Yuchao Jiang, David Hoon, Min Xiao, Brandon Wenz, Nancy R. Zhang, Patricia Brafford, Carol L. Shields, Keith T. Flaherty, Bradley Wubbenhorst, Clemens Krepler, Meenhard Herlyn, Qin Liu


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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31499-7

DOI: 10.1016/j.celrep.2017.10.052

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