title: Tumor associated seizures in glioblastomas are influenced by survival gene expression in a region-specific manner: a gene expression imaging study.
abstract: 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.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States. Electronic address: jlee38@partners.org.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Center for Neuro-oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Norden
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston Children's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States; Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, United States.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Golby
authors.affiliation: Center for Neuro-oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, United States.
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: Department of Biostatistics, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, United States.
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, United States.
authors.forename: William
authors.initials: W
authors.lastname: Wells
authors.affiliation: Castle Biosciences Inc., 3330N 2nd Street, Suite 207, Phoenix, AZ 85012, United States.
authors.forename: Kristen
authors.initials: K
authors.lastname: Oelschlager
authors.affiliation: Castle Biosciences Inc., 3330N 2nd Street, Suite 207, Phoenix, AZ 85012, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Maetzold
authors.affiliation: Center for Neuro-oncology, Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, United States.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D001931:Brain Mapping / Q000379:methods*; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D005909:Glioblastoma / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D012189:Retrospective Studies; D012640:Seizures / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D016019:Survival Analysis; D017741:Survivors; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human; C081781:RTN1 protein, human
keywords: Brain tumor; Gene expression; Imaging; Seizure