Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups - PubMed (original) (raw)

Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups

Sara Dyer et al. Am J Pathol. 2002 Dec.

Abstract

The outcome of pediatric ependymomas is difficult to predict based on clinical and histological parameters. To address this issue, we have performed a comparative genomic hybridization screen of 42 primary and 11 recurrent pediatric ependymomas and correlated the genetic findings with clinical outcome. Three distinct genetic patterns were identified in the primary tumors and confirmed by hierarchical cluster analysis. The first group of structural tumors, showed few, mainly partial imbalances (n = 19). A second numerical group showed 13 or more chromosome imbalances with a nonrandom pattern of whole chromosome gains and losses (n = 5). The remaining tumors (n = 18) showed a balanced genetic profile that was significantly associated with a younger age at diagnosis (P < 0.0001), suggesting that ependymomas arising in infants are biologically distinct from those occurring in older children. Multivariate analysis showed that the structural group had a significantly worse outcome compared to tumors with a numerical (P = 0.05) or balanced profile (P = 0.02). Moreover genetic group and extent of surgical resection contributed significantly to outcome whereas histopathology, age, and other clinical parameters did not. We conclude that patterns of genetic imbalances in pediatric intracranial ependymomas may help to predict clinical outcome.

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Figures

Figure 1.

CGH profiles showing concordant results from two pairs of corresponding fresh (left) and archival formalin-fixed, paraffin-embedded (right) ependymoma specimens. CGH analysis performed using the High Resolution CGH software package (Applied Imaging, Santa Clara, CA). Chromosomal imbalances are recorded at regions where the average test:reference fluorescence ratio (pink lines) and 99.5% confidence intervals (yellow lines) lie outside the standard reference intervals (black lines) for a chromosome or chromosome region. A chromosomal loss is illustrated as a red bar to the immediate left of a chromosome ideogram and a chromosome gain as a green bar to the immediate right of a chromosome ideogram. a: Both fresh and paraffin samples show relative gains at chromosomes 16 and terminal Xq and relative loss at chromosome 22. b: Both fresh and paraffin samples show relative gains at chromosomes 5, 7, 9, 16, 17, 18, 19, and 20.

Figure 2.

Schematic representation of CGH gains and losses in pediatric ependymomas. Each bar corresponds to genomic imbalance in one tumor. Gains and losses are shown on the right and left of each chromosome ideogram, respectively. High-level gains (CGH fluorescence ratio >1.5) are represented as thick bars. a: Structural tumors (n = 19) showing few mainly partial chromosome imbalances. b: Numerical tumors (n = 5) showing many, mainly whole chromosome imbalances.

Figure 3.

Adjusted survival curves for genetic group from multivariate Cox proportional hazards regression analysis using histology, adjuvant therapy, extent of resection, age (<3/>3 years), and tumor location as variables. The structural group is shown by a dotted line, the balanced group by a dashed line, and the numerical group by a solid line. Patients receiving no adjuvant therapy, unknown adjuvant therapy, or chemotherapy alone were removed from this analysis because these groups were too small to be reliably analyzed (n = 11). Structural tumors had a worse outcome than both numerical and balanced tumors (P = 0.05 and 0.02, respectively).

Figure 4.

Adjusted survival curves for 1q status in the posterior fossa tumors from multivariate Cox proportional hazards regression analysis using histology, adjuvant therapy, extent of resection, and age (<3/>3 years) as variables. Tumors with gain of 1q are shown by a dotted line and tumors without gain of 1q are shown by a solid line. Patients receiving no adjuvant therapy, unknown adjuvant therapy, or chemotherapy alone were removed from this analysis because these groups were too small to be reliably analyzed (n = 11). Tumors with gain of 1q had a worse outcome than those without gain of 1q (P = 0.1).

References

1. Ellison DW: Non-astrocytic gliomas. Ellison DW Love S eds. Neuropathology. 1998, chapter 36:pp 36.1-36.10 Mosby, London
1. Grill J, Le Deley MC, Gambarelli D, Raquin MA, Couanet D, Pierre-Kahn A, Habrand JL, Doz F, Frappaz D, Gentet JC, Edan C, Chastagner P, Kalifa C: Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: a multicenter trial of the French Society of Pediatric Oncology. J Clin Oncol 2001, 19:1288-1296 - PubMed
1. Heideman RL, Packer RJ, Albright LA, Freeman CR, Rorke LB: Tumors of the central nervous system. Pizzo PA Poplack DG eds. Principles and Practice of Pediatric Oncology. 1997:pp 633-698 Lippincott-Raven, Philadelphia
1. Duffner PK, Krischer JP, Sanford RA, Horowitz ME, Burger PC, Cohen ME, Friedman HS, Kun LE: Prognostic factors in infants and very young children with intracranial ependymomas. Pediatr Neurosurg 1998, 28:215-222 - PubMed
1. Wiestler OD, Schiffer D, Coons SW, Klug N: Kleihues P Cavenee WK eds. Tumors of the Nervous System 2000. 1996:pp 72-91 IARC, Lyon

Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups - PubMed (original) (raw)