Table 2.
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.