Deep genomic analysis of malignant peripheral nerve sheath tumor cell lines challenges current malignant peripheral nerve sheath tumor diagnosis

Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas of the peripheral nervous system that develop either sporadically or in the context of neurofibromatosis type 1 (NF1). MPNST diagnosis can be challenging and treatment outcomes are poor. We present here a resource consisting...

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Published in:iScience 2023-02, Vol.26 (2), p.106096-106096, Article 106096
Main Authors: Magallón-Lorenz, Miriam, Terribas, Ernest, Ortega-Bertran, Sara, Creus-Bachiller, Edgar, Fernández, Marco, Requena, Gerard, Rosas, Inma, Mazuelas, Helena, Uriarte-Arrazola, Itziar, Negro, Alex, Lausová, Tereza, Castellanos, Elisabeth, Blanco, Ignacio, DeVries, George, Kawashima, Hiroyuki, Legius, Eric, Brems, Hilde, Mautner, Viktor, Kluwe, Lan, Ratner, Nancy, Wallace, Margaret, Fernández-Rodriguez, Juana, Lázaro, Conxi, Fletcher, Jonathan A., Reuss, David, Carrió, Meritxell, Gel, Bernat, Serra, Eduard
Format: Article
Language:English
Subjects:
Biological sciences
Cancer
Neuroscience
Omics
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Summary:Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas of the peripheral nervous system that develop either sporadically or in the context of neurofibromatosis type 1 (NF1). MPNST diagnosis can be challenging and treatment outcomes are poor. We present here a resource consisting of the genomic characterization of 9 widely used human MPNST cell lines for their use in translational research. NF1-related cell lines recapitulated primary MPNST copy number profiles, exhibited NF1, CDKN2A, and SUZ12/EED tumor suppressor gene (TSG) inactivation, and presented no gain-of-function mutations. In contrast, sporadic cell lines collectively displayed different TSG inactivation patterns and presented kinase-activating mutations, fusion genes, altered mutational frequencies and COSMIC signatures, and different methylome-based classifications. Cell lines re-classified as melanomas and other sarcomas exhibited a different drug-treatment response. Deep genomic analysis, methylome-based classification, and cell-identity marker expression, challenged the identity of common MPNST cell lines, opening an opportunity to revise MPNST differential diagnosis. [Display omitted] •A comprehensive genomic resource of widely used MPNST cell lines is presented•Genomic, epigenomic, and marker information improve MPNST differential diagnosis•Genomic analysis detected misidentified and misdiagnosed MPNST cell lines•Misdiagnosed cell lines exhibited a different drug-treatment response Biological sciences; Neuroscience; Cancer; Omics
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.106096