Title

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

Document Type

Article

Publication Date

11-14-2017

Keywords

Adult; Aged; Aged, 80 and over; Animals; Cell Line, Tumor; Female; Genome; Heterografts; Humans; MAP Kinase Signaling System; Male; Melanoma; Mice; Middle Aged; Mutation; Oncogenes; Repetitive Sequences, Nucleic Acid; cell lines; massively parallel sequencing; melanoma; patient-derived xenografts

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.

Clinical Institute

Cancer

Department

Oncology

Department

Dermatology

Volume

21

Issue

7

First Page

1936

Last Page

1952

PubMed ID

29141224

Journal Title

Cell Rep

Share

COinS