Table 2.

Comparison of conventional and contemporary murine astrocytoma models

Characteristic		Conventional ECL Models		Contemporary Models
		Mouse Allografts	Human Xenografts	Human Xenografts		Engineered Mice
				PDX	geHC	GEM	nGEM
Host	Intact immune system	Ya				Y	Y
	Faithful microenvironment	Y				Y	Y
	Intact DNA repair	Y	Yb	Yb	Yb	Y	Y
	Host and tumor genomes differ		Y	Y	Y
Tumor	In vitro culture possible	Y	Y	Y	Y		Y
	Subcutaneous growth	Y	Y	Y	Y		Y
	Orthotopic growth	Y	Y	Y	Y	Y	Y
	Histologically faithful	Yc		Y	Y	Y	Y
	Rapid growth kinetics	Y	Y	Y	Y	d	d
	High penetrance	Y	Y	Y	Y	d	d
	Short latency	Y	Y	Y	Y	d	d
	Defined oncogenic mutations	e	e	e	Y	Y	Y
	Straightforward genotype-phenotype comparisons				Y	Y	Y
	Complex genome landscapes	Yf	Y	Y		Yf
	Defined cellular origin				Y	Yg	Y
	Low grade astrocytomas develop			h		Y	Y
	Stochastic malignant progression					Y

^aSome murine ECL are immunogenic and xenografting requires immunodeficient hosts.¹⁹

^bImmunodeficient severe combined immunodeficiency, but not nude mice have genetic DNA repair defects.¹⁸⁷

^cSome murine ECL fail to invade normal brain.¹⁹

^dGrowth kinetics, penetrance, and latency in GEM and nGEM models vary greatly depending on oncogenic mutations and targeted cell type.

^eMutational profiles can be defined by genomic analyses, but genomic complexity renders direct genotype-phenotype correlations difficult.

^fComplex gene rearrangements occur less frequently in murine compared to human tumors.

^gConventional knockout GEM models do not have a defined cellular origin.

^hIDH mutant PDX models of anaplastic oligodendrogliomas, not astrocytomas, have recently been described.^177,179