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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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Hauptverfasser: Magallón-Lorenz, Míriam (VerfasserIn) , Terribas, Ernest (VerfasserIn) , Ortega-Bertran, Sara (VerfasserIn) , Creus-Bachiller, Edgar (VerfasserIn) , Fernández, Marco (VerfasserIn) , Requena, Gerard (VerfasserIn) , Rosas, Inma (VerfasserIn) , Mazuelas, Helena (VerfasserIn) , Uriarte-Arrazola, Itziar (VerfasserIn) , Negro, Alex (VerfasserIn) , Lausová, Tereza (VerfasserIn) , Castellanos, Elisabeth (VerfasserIn) , Blanco, Ignacio (VerfasserIn) , DeVries, George (VerfasserIn) , Kawashima, Hiroyuki (VerfasserIn) , Legius, Eric (VerfasserIn) , Brems, Hilde (VerfasserIn) , Mautner, Viktor (VerfasserIn) , Kluwe, Lan (VerfasserIn) , Ratner, Nancy (VerfasserIn) , Wallace, Margaret (VerfasserIn) , Fernández-Rodriguez, Juana (VerfasserIn) , Lázaro, Conxi (VerfasserIn) , Fletcher, Jonathan A. (VerfasserIn) , Reuss, David (VerfasserIn) , Carrió, Meritxell (VerfasserIn) , Gel, Bernat (VerfasserIn) , Serra, Eduard (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 9 February 2023
In: iScience
Year: 2023, Jahrgang: 26, Heft: 2, Pages: 1-23
ISSN:2589-0042
DOI:10.1016/j.isci.2023.106096
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.isci.2023.106096
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004223001736
Volltext
Verfasserangaben:Miriam Magallón-Lorenz, Ernest Terribas, Sara Ortega-Bertran, Edgar Creus-Bachiller, Marco Fernández, Gerard Requena, Inma Rosas, Helena Mazuelas, Itziar Uriarte-Arrazola, Alex Negro, Tereza Lausová, Elisabeth Castellanos, Ignacio Blanco, George DeVries, Hiroyuki Kawashima, Eric Legius, Hilde Brems, Viktor Mautner, Lan Kluwe, Nancy Ratner, Margaret Wallace, Juana Fernández-Rodriguez, Conxi Lázaro, Jonathan A. Fletcher, David Reuss, Meritxell Carrió, Bernat Gel, and Eduard Serra

MARC

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520 |a 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. 
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