Journal
ACTA NEUROPATHOLOGICA
Volume 123, Issue 5, Pages 727-738Publisher
SPRINGER
DOI: 10.1007/s00401-012-0941-4
Keywords
Infratentorial ependymoma; Expression profiling; Gene expression signature; Prognostic genes; Microarray; Biomarker
Categories
Funding
- Collaborative Ependymoma Research Network (CERN) Foundation
- SPORE from the NIH [5 P50 CA127001-03]
- MD Anderson Cancer Center
- University of Pittsburgh Medical Center
- Children's National Medical Center
- University of California, San Francisco
- St Jude Children's Research Hospital
- Children's Memorial Hospital
- Cincinnati Children's Hospital
- Henry Ford Hospital
- Memorial Sloan Kettering Cancer Centre
- University San Giovanni Battista Torino-Italy
Ask authors/readers for more resources
Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available