A prognostic gene expression signature in infratentorial ependymoma.
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.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
Khalida
K
Wani
Terri S
TS
Armstrong
Elizabeth
E
Vera-Bolanos
Aditya
A
Raghunathan
David
D
Ellison
Richard
R
Gilbertson
Brian
B
Vaillant
Stewart
S
Goldman
Roger J
RJ
Packer
Maryam
M
Fouladi
Ian
I
Pollack
Tom
T
Mikkelsen
Michael
M
Prados
Antonio
A
Omuro
Riccardo
R
Soffietti
Alicia
A
Ledoux
Charmaine
C
Wilson
Lihong
L
Long
Mark R
MR
Gilbert
Ken
K
Aldape
D000293:Adolescent; D000367:Age Factors; D000951:Antigens, Neoplasm / Q000378:metabolism; D002648:Child; D016000:Cluster Analysis; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D030541:Databases, Genetic; D004806:Ependymoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015192:Infratentorial Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D012737:Sex Factors; D016019:Survival Analysis; D055815:Young Adult
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II