Genetic abnormalities detected in ependymomas by comparative genomic hybridisation

Abstract

Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P<0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P<0.0005) in tumours from adults and the spinal region. Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities--gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14--varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively. Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies.

Figure 1

CGH ideograms divided according to histological variant/site: (A) Intracranial classic tumours; (B) Spinal classic tumours; (C) Anaplastic tumours; (D) Myxopapillary tumours. Loss and gain bars are on the left and right sides of each chromosome respectively.

Figure 2

CGH profiles and FISH from case 38. Standard thresholds (A) imply a severely hypodiploid karyotype, but none of the profiles follows the mid-line. This is characteristic of intermediate ploidy cases, and FISH with centromere probes (B) confirms that there were two copies of chromosome 8 (green) in all cells and three copies of chromosome 17 (red) in many. Skewing the midline to the left to give a chromosome 8 profile midway between the gain and loss thresholds (i.e. normal) produces a profile (C) that implies gain of a large number of chromosomes, although distal 22q is still clearly lost. By this interpretation chromosomes 4 and 16 could have two extra copies compared to a single extra copy of the other gained chromosomes, or could be gained in all cells while a smaller proportion of cells have the other gains.

Figure 3

Kaplan–Meier plots showing a significant difference (P=0.0472) in the survival of patients with intracranial classic ependymomas and intracranial anaplastic ependymomas.

Figure 4

Kaplan–Meier plots showing a significant difference (P=0.0492) in the survival of patients with intracranial ependymomas with and without gain of 1q.

Figure 5

Kaplan–Meier plots showing a significant difference (P=0.0032) in the survival of patients with intracranial anaplastic ependymomas with gain of 1q and patients with intracranial classic ependymomas or anaplastic ependymomas without gain of 1q.