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


ABSTRACT: 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.

SUBMITTER: Garman B 

PROVIDER: S-EPMC5709812 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Garman Bradley B   Anastopoulos Ioannis N IN   Krepler Clemens C   Brafford Patricia P   Sproesser Katrin K   Jiang Yuchao Y   Wubbenhorst Bradley B   Amaravadi Ravi R   Bennett Joseph J   Beqiri Marilda M   Elder David D   Flaherty Keith T KT   Frederick Dennie T DT   Gangadhar Tara C TC   Guarino Michael M   Hoon David D   Karakousis Giorgos G   Liu Qin Q   Mitra Nandita N   Petrelli Nicholas J NJ   Schuchter Lynn L   Shannan Batool B   Shields Carol L CL   Wargo Jennifer J   Wenz Brandon B   Wilson Melissa A MA   Xiao Min M   Xu Wei W   Xu Xaiowei X   Yin Xiangfan X   Zhang Nancy R NR   Davies Michael A MA   Herlyn Meenhard M   Nathanson Katherine L KL  

Cell reports 20171101 7


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 subty  ...[more]

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