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PLoS One. 2017 May 26;12(5):e0178322. doi: 10.1371/journal.pone.0178322. eCollection 2017.

Genomic profile of human meningioma cell lines.

Mei Y1, Bi WL1,2,3, Greenwald NF1,2,3, Agar NY1,2, Beroukhim R2,3,4, Dunn GP5, Dunn IF1,4.

Author information

1
Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
2
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
3
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
5
Department of Neurosurgery, Pathology, and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Abstract

Meningiomas, derived from arachnoid cap cells, are the most common intracranial tumor. High-grade meningiomas, as well as those located at the skull base or near venous sinuses, frequently recur and are challenging to manage. Next-generation sequencing is identifying novel pharmacologic targets in meningiomas to complement surgery and radiation. However, due to the lack of in vitro models, the importance and implications of these genetic variants in meningioma pathogenesis and therapy remain unclear. We performed whole exome sequencing to assess single nucleotide variants and somatic copy number variants in four human meningioma cell lines, including two benign lines (HBL-52 and Ben-Men-1) and two malignant lines (IOMM-Lee and CH157-MN). The two malignant cell lines harbored an elevated rate of mutations and copy number alterations compared to the benign lines, consistent with the genetic profiles of high-grade meningiomas. In addition, these cell lines also harbored known meningioma driver mutations in neurofibromin 2 (NF2) and TNF receptor-associated factor 7 (TRAF7). These findings demonstrate the relevance of meningioma cell lines as a model system, especially as tools to investigate the signaling pathways of, and subsequent resistance to, therapeutics currently in clinical trials.

PMID:
28552950
PMCID:
PMC5446134
DOI:
10.1371/journal.pone.0178322
[Indexed for MEDLINE]
Free PMC Article

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