Predicting which children are at risk for ependymoma relapse

Abstract

Ependymomas account for 6-12% of all pediatric intracranial tumors. Despite complete resection and radiation, about 50% of patients relapse and have subsequent dismal prognoses. As no clinical findings reliably forecast tumor recurrence, we sought to determine if gene expression profiling could be used to distinguish patients at high risk for relapse at initial diagnosis, and thereby make them candidates for innovative treatments at an early stage. We extracted RNA from 13 ependymoma specimens: 7 from patients who experienced tumor recurrence, and 6 from patients who have not recurred. RNA was applied to Affymetrix HG-U133 plus 2.0 microarray chips, and microarrays were analyzed with GeneSpring 7.0 and Prediction Analysis of Microarrays (PAM) software. The 3-gene subset of PLEK (pleckstrin), NF-kappaB2 (nuclear factor kappa beta-2), and LOC374491 (TPTE and PTEN homologous inositol phosphatase pseudogene) was identified as the minimal subset capable of accurately distinguishing tumors according to recurrence. In summary, gene expression profiling may be valuable, perhaps in combination with clinical findings identified in some studies, for identifying children at high risk for ependymoma relapse.

Pediatric Ependymoma: Biological Perspectives

“…However, the need to identify new correlates of outcome in pediatric ependymoma has intensified because tumor recurrence can occur in up to 50% of children, despite complete surgical resection and adjuvant radiotherapy, with only approximately 15% of patients subsequently surviving beyond 5 years (2,14,15,21).…”

“…However, although complete resection is the most consistently reported favorable clinical prognostic factor (1,(16)(17)(18), this is not a universal finding and some studies fail to show this relationship for pediatric posterior fossa tumors (19,20). Furthermore, despite complete excision, local tumor recurrence can develop in up to 50% of cases, even following adjuvant radiotherapy (14,15,21).…”

Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma

“…Treatment and prognostication is predominantly currently based on clinical criteria despite many genomic studies identifying common molecular aberrations (Reardon et al, 1999;Zheng et al, 2000;Scheil et al, 2001;Ward et al, 2001;Carter et al, 2002;Dyer et al, 2002;Grill et al, 2002;Jeuken et al, 2002;Gilhuis et al, 2004;Taylor et al, 2005;SuarezMerino et al, 2005;Mendrzyk et al, 2006;Modena et al, 2006;Sowar et al, 2006;Lukashova-v Zangen et al, 2007). Currently complete tumour resection is the only confirmed independent prognostic marker, indicating a better patient outcome (Bouffet et al, 1998;Sala et al, 1998).…”

PI3K Pathway Activation Provides a Novel Therapeutic Target for Pediatric Ependymoma and Is an Independent Marker of Progression-Free Survival

“…The extent of surgical resection is still the most consistent marker of outcome (11,12). However, even with complete resection, tumor recurrence occurs in up to 50% of patients (13). A number of putative biologic and genomic prognostic markers have been identified in large cohorts, including nucleolin (14), Ki67 (15), 1q gain (16), nestin (17), Nell2, and Lama2 (18).…”