Diversity of cytogenetic and pathohistologic profiles in glioblastoma.
We present a small series of patients with primary glioblastoma multiforme (GBM), and combine individual genetic data with pathohistologic characteristics and clinical outcome. Eighteen patients (12 men, 6 women, median age 51 years) with histologically proven GBM underwent surgical debulking followed by radiotherapy. Fifteen received concomitant chemotherapy. Histologic typing, immunohistochemistry for CD34, karyotypic analysis, and classification of the pattern of neovascularization was done in all patients. In 12/18, we performed methylation-specific polymerase chain reaction of the MGMT gene (O-6-methylguanine-DNA methyltransferase). The survival duration of patients spanned 3-58 months. By classical banding methods, 15/18 patients showed at least one aberration characteristic for primary glioblastoma (+7 in 7/18, deletions of 9p in 10/18 and -10 or deletions from 10q in 8/18 patients). We could not assess whether patients who survived for longer periods showed less complex or fewer aberrations than the patients who survived less than one year. Losses of 6p21(VEGF), 4q27(bFGF), and 12p11 approximately p13 (ING4) were associated with the "bizarre" pattern of neoangiogenesis. Methylation of the MGMT promoter was found in 3/12 patients. Even in this small series, the main characteristic of GBM was its diversity regarding all investigated histologic and genetic characteristics. This extreme diversity should be considered in the design of targeted therapies in GBM.
Hassler
Marco
M
Department of Internal Medicine I, Clinical Division of Oncology, Medical University Vienna, 6i, Währinger Gürtel 18-20, A-1097 Vienna, Austria.
Seidl
Sonja
S
Fazeny-Doerner
Barbara
B
Preusser
Matthias
M
Hainfellner
Johannes
J
Rössler
Karl
K
Prayer
Daniela
D
Marosi
Christine
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D002869:Chromosome Aberrations; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D020868:Gene Silencing; D014644:Genetic Variation; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009389:Neovascularization, Pathologic; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019853:O(6)-Methylguanine-DNA Methyltransferase