Specific Genetic Predictors of Chemotherapeutic Response and Survival in Patients With Anaplastic Oligodendrogliomas

Abstract

Allelic loss (or loss of heterozygosity) of chromosome 1p is a statistically significant predictor of chemosensitivity, and combined loss involving chromosomes 1p and 19q is statistically significantly associated with both chemosensitivity and longer recurrence-free survival after chemotherapy. Moreover, in both univariate and multivariate analyses, losses involving both chromosomes 1p and 19q were strongly associated with longer overall survival, whereas CDKN2A gene deletions and ring enhancement (i.e., contrast enhancement forming a rim around the tumor) on neuroimaging were associated with a significantly worse prognosis. The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma. These results suggest that molecular genetic analysis may aid therapeutic decisions and predict outcome in patients with anaplastic oligodendrogliomas.

DNA replication licensing and cell cycle kinetics of oligodendroglial tumours

“…The presence of 1p/19q loss predicts a longer progression-free survival and a better response to combination chemotherapy (Cairncross et al, 1998;Smith et al, 2000;Ino et al, 2001). Similar cytogenetic abnormalities are observed in tumours which also have areas of astrocytic differentiation (Kraus et al, 1995;Maintz et al, 1997).…”

Hypermethylation and transcriptional downregulation of the CITED4 gene at 1p34.2 in oligodendroglial tumours with allelic losses on 1p and 19q

“…Recent data indicate that these combined 1p and 19q losses are mediated by an unbalanced t(1;19)(q10;p10) translocation (Griffin et al, 2006;Jenkins et al, 2006). Importantly, 1p/19q deletion is associated with favourable response to radioand chemotherapy as well as prolonged survival (Cairncross et al, 1998(Cairncross et al, , 2006van den Bent et al, 2006). Thus, molecular testing for these losses provides clinically valuable information beyond the conventional histologic classification.…”

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype

“…Allelic alterations of chromosomes 1 and 19 are frequent events in human di use gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al, 1998;Smith et al, submitted). Using 115 human di use gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes.…”

“…In a recent retrospective analysis, Cairncross et al (1998) used a set of 39 anaplastic oligodendrogliomas to demonstrate that allelic loss of the chromosome 1 p-arm is a strong predictor of chemotherapeutic response. They further demonstrated in the same set of anaplastic oligodendrogliomas that combined loss of chromosome arms 1p and 19q is associated with both chemotherapeutic response and prolonged recurrence-free survival post-chemotherapy.…”