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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Detalhes bibliográficos
Autores: 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 Rodríguez, Juana, Lázaro García, Conxi, Fletcher, Jonathan A., Reuss, David E., Carrió, Meritxell, Gel Moreno, Bernat, Serra Arenas, Eduard
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/200047
Acesso em linha:https://hdl.handle.net/2445/200047
Access Level:acceso abierto
Palavra-chave:Neurofibromatosi
Genòmica
Càncer
Neurofibromatosis
Genomics
Cancer
Descrição
Resumo: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 suppres-sor 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 muta-tional frequencies and COSMIC signatures, and different methylome-based clas-sifications. 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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