Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

Abstract

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.

A practical review of prognostic correlations of molecular biomarkers in glioblastoma

“…Loss of heterozygosity of 10q23, where PTEN resides, has been shown to correlate with OS in some studies 23,51 but not others. 8,10 These findings suggest additional mechanisms govern PTEN signaling.…”

Promoter methylation and expression analysis of MGMT in advanced pediatric brain tumors

“…At present, there is an ongoing phase I/II study of TMZ plus autologous stem cell rescue in therapy of children with newly diagnosed HGG or recurrent brain tumors by Dr Henry Friedman of the Duke Comprehensive Cancer Center in Durham, NC, USA. The use of TMZ alone or combined has produced promising results in phase I/II clinical trials in adult high grade gliomas (HGG) (26)(27)(28)(29)(30). A recent study on a small cohort of recurrent or progressive gliomas in adults pre-treated with TMZ showed a reduction of side effects and an objective response respect to other more aggressive treatments (31).…”

Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

“…20 -22 In turn, genomic deletions of chromosomes 9 and 10 at regions that harbor tumor suppressor genes are also typically found in glioblastomas, where they have been associated with the development of the tumor, its progression, and a poor prognosis. [23][24][25][26] Interestingly, monosomy 10 is associated with gain or amplification of the EGFR gene on chromosome 7p11.2, supporting the role of both alterations in gliomagenesis. 27,28 Other genetic abnormalities that can be frequently found in low-grade gliomas 29,30 [eg, combined del(1p)/ del(19q) and TP53 mutation] are less frequently detected in glioblastomas.…”