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

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

  • iScience. 2023 Jan 31;26(2):106096. doi: 10.1016/j.isci.2023.106096.
Miriam Magallón-Lorenz 1,  Ernest Terribas 1,  Sara Ortega-Bertran 2 3,  Edgar Creus-Bachiller 2 3 4,  Marco Fernández 5,  Gerard Requena 5,  Inma Rosas 6 7,  Helena Mazuelas 1,  Itziar Uriarte-Arrazola 1,  Alex Negro 6 7,  Tereza Lausová 8 9,  Elisabeth Castellanos 6 7,  Ignacio Blanco 6 10,  George DeVries 11,  Hiroyuki Kawashima 12,  Eric Legius 13,  Hilde Brems 13,  Viktor Mautner 14,  Lan Kluwe 14,  Nancy Ratner 15,  Margaret Wallace 16,  Juana Fernández-Rodriguez 2 3 4,  Conxi Lázaro 2 3 4,  Jonathan A Fletcher 17,  David Reuss 8 9,  Meritxell Carrió 1,  Bernat Gel 1 18,  Eduard Serra 1 4
Affiliations

Affiliations

  • 1 Hereditary Cancer Group, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916 Badalona, Barcelona, Spain.
  • 2 Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, 08098 Barcelona, Spain.
  • 3 Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
  • 4 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • 5 Cytometry Core Facility, Germans Trias & Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.
  • 6 Clinical Genomics Research Group, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916 Badalona, Barcelona, Spain.
  • 7 Clinical Genomics Unit, Clinical Genetics Service, Northern Metropolitan Clinical Laboratory, Germans Trias i Pujol University Hospital (HGTP), Can Ruti Campus, 08916 Badalona, Barcelona, Spain.
  • 8 Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
  • 9 Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
  • 10 Genetic Counseling Unit, Clinical Genetics Service, Northern Metropolitan Clinical Laboratory, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
  • 11 Hines VA Hospital, Hines, IL 60141, USA.
  • 12 Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Palliative Care Team, Niigata University Medical and Dental Hospital, Niigata, Japan.
  • 13 Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • 14 Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • 15 Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 16 Department of Molecular Genetics & Microbiology, and UF Health Cancer Center, University of Florida College of Medicine, Gainesville, FL, USA.
  • 17 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 528, Boston, MA 02115, USA.
  • 18 Departament de Fonaments Clínics, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), 08036 Barcelona, Spain.
PMID: 36818284 DOI: 10.1016/j.isci.2023.106096
Abstract

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.

Keywords

Biological sciences; Cancer; Neuroscience; Omics.

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