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Tumor Associated Seizures in Glioblastomas are Influenced by Survival Gene Expression in a Region-specific Manner: A Gene Expression Imaging Study

Institution:
1Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jlee38@partners.org.
2Center for Neuro-oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
3Department of Pathology, Brigham and Women’s Hospital, Boston Children’s Hospital, and Harvard Medical School, Boston, MA, USA.
4Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
5Department of Biostatistics, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
6Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
7Castle Biosciences, Inc., Phoenix, AZ, USA.
Publisher:
Elsevier Science
Publication Date:
Jul-2014
Journal:
Epilepsy Res
Volume Number:
108
Issue Number:
5
Pages:
843-52
Citation:
Epilepsy Res. 2014 Jul;108(5):843-52.
PubMed ID:
24690158
PMCID:
PMC4076930
Keywords:
Brain tumor, Gene expression, Imaging, Seizure
Appears in Collections:
NCIGT, NAC, SLICER, SPL
Sponsors:
P41 EB015902/EB/NIBIB NIH HHS/United States
P41 RR013218/RR/NCRR NIH HHS/United States
P41 EB015898/EB/NIBIB NIH HHS/United States
P41 RR019703/RR/NCRR NIH HHS/United States
Generated Citation:
Lee J.W., Norden A.D., Ligon K.L., Golby A.J., Beroukhim R., Quackenbush J., Wells III W.M., Oelschlager K., Maetzold D., Wen P.Y. Tumor Associated Seizures in Glioblastomas are Influenced by Survival Gene Expression in a Region-specific Manner: A Gene Expression Imaging Study. Epilepsy Res. 2014 Jul;108(5):843-52. PMID: 24690158. PMCID: PMC4076930.
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Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs. 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs. 32.7 months, p=0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

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