Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification
Menée sur trois cohortes européennes incluant 189 patients pédiatriques atteints d'un épendymome, cette étude évalue l'association entre un gain du chromosome 1q25 et la survie des patients
Purpose: The high incidence of recurrence and unpredictable clinical outcome for pediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. We therefore evaluated 1q25 gain across three age and treatment defined European clinical trial cohorts of pediatric intracranial ependymoma. Experimental Design: Frequency of 1q gain was assessed across 48 ependymomas (42 primary, 6 recurrent) using Affymetrix® 500K SNP arrays. Gain of 1q25 was then evaluated by interphase FISH across 189 tumors treated on the CCLG/SIOP CNS9204 (n=60) and BBSFOP (n=65) adjuvant chemotherapy trials, or with primary post-operative radiotherapy (SIOP CNS9904/RT, n=64). Results were correlated with clinical, histological and survival data. Results: Gain of 1q was the most frequent imbalance in primary (7/42, 17 %) and recurrent ependymomas (2/6, 33 %). Gain of 1q25 was an independent predictor of tumor progression across the pooled trial cohort (HR 2.55, 95 % CIs 1.56 - 4.16, p=0.0002) and both CNS9204 (HR 4.03 (1.88 - 8.63)) and BBSFOP (HR 3.10 (1.22 - 7.86)) groups. The only clinical variable associated with adverse outcome was incomplete tumor resection. Integrating tumor resectability with 1q25 status enabled stratification of cases into disease progression risk groups for all three trial cohorts. Conclusions: This is the first study to validate a prognostic genomic marker for childhood ependymoma across independent trial groups. 1q25 gain predicts disease progression and can contribute to patient risk stratification. We advocate the prospective evaluation of 1q25 gain as an adverse marker in future international clinical trials.
Clinical Cancer Research , résumé, 2012