Patients with high-grade gliomas harboring deletions of chromosomes 9p and 10q benefit from temozolomide treatment.
Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ) chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group) and 30 patients received radiotherapy alone (RT group). The most common aberrations detected were gains of parts of chromosome 7 and losses of 10q, 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months). Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.
Wemmert
Silke
S
Institute of Human Genetics, Saarland University, Homburg/Saar D-66421, Germany.
Ketter
Ralf
R
Rahnenführer
Jörg
J
Beerenwinkel
Niko
N
Strowitzki
Martin
M
Feiden
Wolfgang
W
Hartmann
Christian
C
Lengauer
Thomas
T
Stockhammer
Florian
F
Zang
Klaus D
KD
Meese
Eckart
E
Steudel
Wolf-Ingo
WI
von Deimling
Andreas
A
Urbschat
Steffi
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy*; D002872:Chromosome Deletion; D002875:Chromosomes / Q000648:ultrastructure; D002879:Chromosomes, Human, Pair 10; D002899:Chromosomes, Human, Pair 9; D003582:Cytogenetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D005909:Glioblastoma; D005910:Glioma / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D009693:Nucleic Acid Hybridization; D010232:Paraffin / Q000737:chemistry; D011379:Prognosis; D016016:Proportional Hazards Models; D012737:Sex Factors; D000077204:Temozolomide; D013997:Time Factors; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D005819:Genetic Markers; D003606:Dacarbazine; D010232:Paraffin; D000077204:Temozolomide