Deep genomic analysis of malignant peripheral nerve sheath tumor cell lines challenges current malignant peripheral nerve sheath tumor diagnosis
oleh: 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, Eduard Serra
| Format: | Article |
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| Diterbitkan: | Elsevier 2023-02-01 |
Deskripsi
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.