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Naslov:Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model : in situ detection of 2-HG and [alpha]-KG
Avtorji:ID Navis, Anna C. (Avtor)
ID Niclou, Simone P. (Avtor)
ID Fack, Fred (Avtor)
ID Stieber, Daniel (Avtor)
ID Lith, Sanne A. M. van (Avtor)
ID Verrijp, Kiek (Avtor)
ID Wright, Alan F. (Avtor)
ID Stauber, Jonathan (Avtor)
ID Tops, Bastiaan (Avtor)
ID Otte-Holler, Irene (Avtor)
ID Wevers, Ron A. (Avtor)
ID Rooij, Arno van (Avtor)
ID Pusch, Stefan (Avtor)
ID Deimling, Andreas von (Avtor)
ID Tigchelaar, Wikky (Avtor)
ID Noorden, Cornelis J. F. van (Avtor)
ID Wesseling, Pieter (Avtor)
ID Leenders, William P. J. (Avtor)
Datoteke:URL URL - Izvorni URL, za dostop obiščite https://doi.org/10.1186/2051-5960-1-18
 
.pdf PDF - Predstavitvena datoteka, prenos (1,76 MB)
MD5: DD7DE412BB3AF3306FA8C35B5B862A13
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo NIB - Nacionalni inštitut za biologijo
Povzetek:Background Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level. Results LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis. Conclusions The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations.
Ključne besede:gliomaI, IDH mutations, xenograft, D-2-hydroxyglutarate, [alpha]-ketoglutarate, mitochondria: LESA-nano ESI-FTIC
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Datum objave:29.05.2013
Leto izida:2013
Št. strani:str. 1-12
Številčenje:Vol. 1
PID:20.500.12556/DiRROS-20026 Novo okno
UDK:577.2
ISSN pri članku:2051-5960
DOI:10.1186/2051-5960-1-18 Novo okno
COBISS.SI-ID:4651599 Novo okno
Opomba:Nasl. z nasl. zaslona; Opis vira z dne 19. 3. 2018;
Datum objave v DiRROS:02.08.2024
Število ogledov:468
Število prenosov:314
Metapodatki:XML DC-XML DC-RDF
:
NAVIS, Anna C., NICLOU, Simone P., FACK, Fred, STIEBER, Daniel, LITH, Sanne A. M. van, VERRIJP, Kiek, WRIGHT, Alan F., STAUBER, Jonathan, TOPS, Bastiaan, OTTE-HOLLER, Irene, WEVERS, Ron A., ROOIJ, Arno van, PUSCH, Stefan, DEIMLING, Andreas von, TIGCHELAAR, Wikky, NOORDEN, Cornelis J. F. van, WESSELING, Pieter in LEENDERS, William P. J., 2013, Increased mitochondrial activity in a novel IDH1-R132H mutant human oligodendroglioma xenograft model : in situ detection of 2-HG and [alpha]-KG. Acta neuropathologica communications [na spletu]. 2013. Vol. 1, p. 1–12. [Dostopano 6 april 2025]. DOI 10.1186/2051-5960-1-18. Pridobljeno s: https://dirros.openscience.si/IzpisGradiva.php?lang=slv&id=20026
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Gradivo je del revije

Naslov:Acta neuropathologica communications
Skrajšan naslov:Acta Neuropathol. Commun.
Založnik:BioMed Central
ISSN:2051-5960
COBISS.SI-ID:522939929 Novo okno

Gradivo je financirano iz projekta

Financer:Drugi - Drug financer ali več financerjev
Številka projekta:2010(1)- 01
Naslov:the Hersenstichting
Financer:Drugi - Drug financer ali več financerjev
Program financ.:FNR in Luxembourg
Številka projekta:C10/BM/784322
Naslov:ESCAPE
Akronim:CORE
Financer:Drugi - Drug financer ali več financerjev
Akronim:RUNMC

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