학술논문
Deep genomic analysis of malignant peripheral nerve sheath tumor cell lines challenges current malignant peripheral nerve sheath tumor diagnosis
Document Type
article
Author
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
Source
iScience, Vol 26, Iss 2, Pp 106096- (2023)
Subject
Language
English
ISSN
2589-0042
Abstract
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.