Genetic aberrations in gliomatosis cerebri.
OBJECTIVE
Identifying the genetic alterations in gliomatosis cerebri (GC) may yield clinically useful prognostic markers and provide clues as to whether GC represents a distinct pathological entity or is an extreme form of diffusely infiltrative glioma.


METHODS
Clinical histories, treatment histories, magnetic resonance imaging, and pathological analysis of patients with GC treated at either the University of California San Francisco or the Mayo Clinic were reviewed. Degenerate oligonucleotide-primed polymerase chain reaction was performed on biopsy samples of GC. Comparative genomic hybridization was used to determine relative deoxyribonucleic acid copy number. We evaluated relationships of clinical and radiological treatment and comparative genomic hybridization data to survival after diagnosis with Cox regression analysis.


RESULTS
Radiographic analysis and biopsy specimens were available for study in 29 patients (17 men, 12 women). Comparative genomic hybridization was successfully performed in 22 patients. Contrast enhancement was the most significant predictor of poor survival (P = 0.0026). Loss of chromosomes 13q and 10q and gains of 7q were also independent significant predictors of poor survival (P = 0.0032, 0.0335, and 0.0487, respectively). Patients treated with temozolomide or with radiation therapy had improved survival, but this effect did not reach statistical significance (P = 0.180 and 0.124, respectively).


CONCLUSIONS
Chromosomal aberrations associated with aggressive astrocytomas are predictors of poor outcome in patients with GC. This suggests that GC may be an architectural variant of diffuse astrocytomas. The presence of these aberrations and the presence of any contrast enhancement on magnetic resonance imaging scans are possible stratifiers for patients with GC. Stratification of GC into higher- and lower-grade forms may be useful in tailoring treatments to patients with this disease.
Ware
Marcus L
ML
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA. marcusware@gmail.com
Hirose
Yuichi
Y
Scheithauer
Bernd W
BW
Yeh
Ru-Fang
RF
Mayo
Mary C
MC
Smith
Justin S
JS
Chang
Susan
S
Cha
Soonmee
S
Tihan
Tarik
T
Feuerstein
Burt G
BG
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018302:Neoplasms, Neuroepithelial / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000235:genetics; D012189:Retrospective Studies