A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.
Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may...
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2013
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oai:doaj.org-article:0fde4b9e5f4a4bf1977638549aa2787d2021-11-18T07:52:47ZA novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.1932-620310.1371/journal.pone.0059773https://doaj.org/article/0fde4b9e5f4a4bf1977638549aa2787d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527265/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.Barbara KlinkHrvoje MileticDaniel StieberPeter C HuszthyJaime Alberto Campos ValenzuelaJörg BalssJian WangManja SchubertPer Øystein SakariassenTerje SundstrømAnja TorsvikMads AarhusRupavathana MahesparanAndreas von DeimlingLars KaderaliSimone P NiclouEvelin SchröckRolf BjerkvigJanice M NigroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59773 (2013) |
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Medicine R Science Q |
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Medicine R Science Q Barbara Klink Hrvoje Miletic Daniel Stieber Peter C Huszthy Jaime Alberto Campos Valenzuela Jörg Balss Jian Wang Manja Schubert Per Øystein Sakariassen Terje Sundstrøm Anja Torsvik Mads Aarhus Rupavathana Mahesparan Andreas von Deimling Lars Kaderali Simone P Niclou Evelin Schröck Rolf Bjerkvig Janice M Nigro A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. |
| description |
Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment. |
| format |
article |
| author |
Barbara Klink Hrvoje Miletic Daniel Stieber Peter C Huszthy Jaime Alberto Campos Valenzuela Jörg Balss Jian Wang Manja Schubert Per Øystein Sakariassen Terje Sundstrøm Anja Torsvik Mads Aarhus Rupavathana Mahesparan Andreas von Deimling Lars Kaderali Simone P Niclou Evelin Schröck Rolf Bjerkvig Janice M Nigro |
| author_facet |
Barbara Klink Hrvoje Miletic Daniel Stieber Peter C Huszthy Jaime Alberto Campos Valenzuela Jörg Balss Jian Wang Manja Schubert Per Øystein Sakariassen Terje Sundstrøm Anja Torsvik Mads Aarhus Rupavathana Mahesparan Andreas von Deimling Lars Kaderali Simone P Niclou Evelin Schröck Rolf Bjerkvig Janice M Nigro |
| author_sort |
Barbara Klink |
| title |
A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. |
| title_short |
A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. |
| title_full |
A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. |
| title_fullStr |
A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. |
| title_full_unstemmed |
A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1. |
| title_sort |
novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in fubp1, cic, and idh1. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/0fde4b9e5f4a4bf1977638549aa2787d |
| work_keys_str_mv |
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