On the origin of glioma

Figures & data

Table I. Mouse models with confirmed or candidate cell of origin for glioma.

Cell of origin	Promoter	Deleted or inactivated genes	Overexpressed or activated genes	Ref
Astrocyte	NA	p16^Ink4a and p19^Arf	Mutant EGFR	(29)
	GFAP		v-Src	(30)
	GFAP		Ha-Ras	(31)
	GFAP	pRb, p107, p130		(32)
	GFAP (RCAS-tv-a)		PDGF-B	(21)
Neural stem or progenitor cell	Nestin-CreERT2	Nf1, p53, and/or Pten		(63)
	GFAP-Cre		H-Ras and Akt	(24)
	Nestin (RCAS-tv-a)		K-Ras and Akt	(64)
	NA	p16^Ink4a and p19^Arf	Mutant EGFR	(29)
Oligodendrocyte precursor cell	NA	p53	Ras	(74)
	CNP (RCAS-tv-a)		PDGF-B	(8)
	S100β		Mutant EGFR	(6)
	GFAP-Cre or Nestin-Cre	Nf1 and p53		(7)

NA = not applicable.

Figure 1. Putative glioma cell of origin and its role for glioma development. A: A simplified schematic representation of glial cell development from the multipotent CNS stem cell into astrocytes and oligodendrocytes, where each stage is defined by the expression of markers. Red lightings indicate the occurrence of an oncogenic event that will induce glioma development. B: The role of cellular origin for glioma initiation, progression, recurrence and response to therapy remains largely unknown. The search for biomarkers that could distinguish phenotypically distinct glioma subgroups based on cell of origin could be one path towards elucidating this matter. NSC = neural stem cell; GRPC = glial restricted progenitor cell; APC = astrocyte precursor cell; OPC = oligodendrocyte precursor cell.

Bachoo RM, Maher EA, Ligon KL, Sharpless NE, Chan SS, You MJ, Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell. 2002;1:269–77.

 PubMed Web of Science ®Google Scholar

Weissenberger J, Steinbach JP, Malin G, Spada S, Rulicke T, Aguzzi A. Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene. 1997;14:2005–13.

 PubMed Web of Science ®Google Scholar

Ding H, Roncari L, Shannon P, Wu X, Lau N, Karaskova J, Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res. 2001;61:3826–36.

 PubMed Web of Science ®Google Scholar

Xiao A, Wu H, Pandolfi PP, Louis DN, Van Dyke T. Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell. 2002;1:157–68.

 PubMed Web of Science ®Google Scholar

Dai C, Celestino JC, Okada Y, Louis DN, Fuller GN, Holland EC. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 2001;15:1913–25.

 PubMed Web of Science ®Google Scholar

Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK, Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell. 2009;15:45–56.

 PubMed Web of Science ®Google Scholar

Marumoto T, Tashiro A, Friedmann-Morvinski D, Scadeng M, Soda Y, Gage FH, Development of a novel mouse glioma model using lentiviral vectors. Nat Med. 2009;15:110–16.

 PubMed Web of Science ®Google Scholar

Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet. 2000;25:55–7.

 PubMed Web of Science ®Google Scholar

Hide T, Takezaki T, Nakatani Y, Nakamura H, Kuratsu J, Kondo T. Combination of a ptgs2 inhibitor and an epidermal growth factor receptor-signaling inhibitor prevents tumorigenesis of oligodendrocyte lineage-derived glioma-initiating cells. Stem Cells. 2011;29:590–9.

 PubMedGoogle Scholar

Lindberg N, Kastemar M, Olofsson T, Smits A, Uhrbom L. Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma. Oncogene. 2009;28:2266–75.

 PubMed Web of Science ®Google Scholar

Persson AI, Petritsch C, Swartling FJ, Itsara M, Sim FJ, Auvergne R, Non-stem cell origin for oligodendroglioma. Cancer Cell. 2010;18:669–82.

 PubMed Web of Science ®Google Scholar

Liu C, Sage JC, Miller MR, Verhaak RG, Hippenmeyer S, Vogel H, Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 2011;146:209–21.

 PubMed Web of Science ®Google Scholar