Although ependymomas – a group of CNS tumours – have a similar appearance in affected patients, who are mostly children, the underlying genetic alterations and clinical outcomes vary depending on the location of the tumour, hindering the development of useful animal models. Using cross-species genomics, Johnson et al. have now broken through this barrier. They compared the transcriptomes of subgroups of human ependymoma with those of spatially and developmentally distinct groups of mouse neural stem cells (NSCs), and found a close match between a subset of human supratentorial ependymomas and embryonic cerebral NSCs from mice with deletion of the tumour suppressor gene Ink4a/Arf. The human tumours were also found to have amplification and/or overex-pression of EphB2, the product of which is involved in numerous developmental processes. When the matched mouse NSCs were transduced with EphB2 and transplanted into the mouse forebrain, tumours that were histologically and molecularly identical to the human ependymomas resulted, with high penetrance. This approach could be used to develop models for other ependymoma subgroups, potentially helping to attain a cure for this often-incurable set of diseases.

Johnson
RA
,
Wright
KD
,
Poppleton
H
,
Mohankumar
KM
,
Finkelstein
D
,
Pounds
SB
,
Rand
V
,
Leary
SE
,
White
E
,
Eden
C
, et al. 
(
2010
).
Cross-species genomics matches driver mutations and cell compartments to model ependymoma
.
Nature
466
,
632
636
.