Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new...

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Autores principales:	Jody Fromm Longo, Stephanie N. Brosius, Iya Znoyko, Victoria A. Alers, Dorea P. Jenkins, Robert C. Wilson, Andrew J. Carroll, Daynna J. Wolff, Kevin A. Roth, Steven L. Carroll
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f5187e91b33a4aedba5946cbbbfb1198
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spelling	oai:doaj.org-article:f5187e91b33a4aedba5946cbbbfb11982021-12-02T13:33:45ZEstablishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line10.1038/s41598-021-85055-22045-2322https://doaj.org/article/f5187e91b33a4aedba5946cbbbfb11982021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85055-2https://doaj.org/toc/2045-2322Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new sporadic MPNST cell line, 2XSB, which shares the molecular and genomic features of the parent tumor. These cells have a highly complex karyotype with extensive chromothripsis. 2XSB cells show robust invasive 3-dimensional and clonogenic culture capability and form solid tumors when xenografted into immunodeficient mice. High-density single nucleotide polymorphism array and whole exome sequencing analyses indicate that, unlike NF1-associated MPNSTs, 2XSB cells have intact, functional NF1 alleles with no evidence of mutations in genes encoding components of Polycomb Repressor Complex 2. However, mutations in other genes implicated in MPNST pathogenesis were identified in 2XSB cells including homozygous deletion of CDKN2A and mutations in TP53 and PTEN. We also identified mutations in genes not previously associated with MPNSTs but associated with the pathogenesis of other human cancers. These include DNMT1, NUMA1, NTRK1, PDE11A, CSMD3, LRP5 and ACTL9. This sporadic MPNST-derived cell line provides a useful tool for investigating the biology and potential treatment regimens for sporadic MPNSTs.Jody Fromm LongoStephanie N. BrosiusIya ZnoykoVictoria A. AlersDorea P. JenkinsRobert C. WilsonAndrew J. CarrollDaynna J. WolffKevin A. RothSteven L. CarrollNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jody Fromm Longo Stephanie N. Brosius Iya Znoyko Victoria A. Alers Dorea P. Jenkins Robert C. Wilson Andrew J. Carroll Daynna J. Wolff Kevin A. Roth Steven L. Carroll Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
description	Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new sporadic MPNST cell line, 2XSB, which shares the molecular and genomic features of the parent tumor. These cells have a highly complex karyotype with extensive chromothripsis. 2XSB cells show robust invasive 3-dimensional and clonogenic culture capability and form solid tumors when xenografted into immunodeficient mice. High-density single nucleotide polymorphism array and whole exome sequencing analyses indicate that, unlike NF1-associated MPNSTs, 2XSB cells have intact, functional NF1 alleles with no evidence of mutations in genes encoding components of Polycomb Repressor Complex 2. However, mutations in other genes implicated in MPNST pathogenesis were identified in 2XSB cells including homozygous deletion of CDKN2A and mutations in TP53 and PTEN. We also identified mutations in genes not previously associated with MPNSTs but associated with the pathogenesis of other human cancers. These include DNMT1, NUMA1, NTRK1, PDE11A, CSMD3, LRP5 and ACTL9. This sporadic MPNST-derived cell line provides a useful tool for investigating the biology and potential treatment regimens for sporadic MPNSTs.
format	article
author	Jody Fromm Longo Stephanie N. Brosius Iya Znoyko Victoria A. Alers Dorea P. Jenkins Robert C. Wilson Andrew J. Carroll Daynna J. Wolff Kevin A. Roth Steven L. Carroll
author_facet	Jody Fromm Longo Stephanie N. Brosius Iya Znoyko Victoria A. Alers Dorea P. Jenkins Robert C. Wilson Andrew J. Carroll Daynna J. Wolff Kevin A. Roth Steven L. Carroll
author_sort	Jody Fromm Longo
title	Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
title_short	Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
title_full	Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
title_fullStr	Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
title_full_unstemmed	Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
title_sort	establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f5187e91b33a4aedba5946cbbbfb1198
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Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line

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