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
  • 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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