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

Autor: Longo JF; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA., Brosius SN; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294-0017, USA.; Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, 35294-0017, USA.; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA., Znoyko I; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA., Alers VA; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA., Jenkins DP; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA., Wilson RC; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA.; Center for Genomic Medicine, Medical University of South Carolina, Charleston, SC, 29425-9080, USA., Carroll AJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294-0017, USA., Wolff DJ; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA., Roth KA; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Carroll SL; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, MSC 908, Charleston, SC, 29425-9080, USA. carrolst@musc.edu.; Center for Genomic Medicine, Medical University of South Carolina, Charleston, SC, 29425-9080, USA. carrolst@musc.edu.; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294-0017, USA. carrolst@musc.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Mar 11; Vol. 11 (1), pp. 5690. Date of Electronic Publication: 2021 Mar 11.
DOI: 10.1038/s41598-021-85055-2
Abstrakt: 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.
Databáze: MEDLINE
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