Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors

Abstract

Deletions on chromosomes 1p and 19q are associated with favorable prognosis in patients with oligodendroglial tumors. The aim of our study was to identify additional genomic aberrations linked to patient survival. We performed a genome‐wide screen for genomic imbalances by comparative genomic hybridization on tumors from 70 patients, including 40 oligodendrogliomas, 30 oligoastrocytomas (21 WHO grade II tumors, 49 WHO grade III tumors). Data were correlated with overall patient survival (OS, median follow‐up: 5.8 years). The most frequent aberrations were losses on chromosome 19q (64%), 1p (59%), 9p (26%), 4q (21%), 10q (19%), 18q (17%); gains on 7q (24%), 19p (19%), 7p (17%). In univariate analyses, combined 1p/19q and 19q loss were significantly associated with longer OS, and gains on 7, 8q, 19q, 20, losses on 9p, 10, 18q, Xp with shorter OS. Multivariate analyses showed the most significant prognostic factors for OS of patients with any oligodendroglial tumor to be WHO grade [odds ratio (OR) 8], 7p gain (OR 6), 9p loss (OR 3); for OS of patients with anaplastic tumors to be 7p gain (OR 10), 8q gain (OR 5), 18q loss (OR 3). Patients with anaplastic oligodendroglial tumors containing one or more prognostically unfavorable genomic aberration had a poor outcome independent of the 1p/19q status. In summary, we identified several independent genomic markers of shorter survival in patients with oligodendroglial tumors. Thus, molecular diagnostic testing, which is usually restricted to 1p/19q deletion analysis, may need to be refined by additionally assessing the prognostically unfavorable genomic aberrations identified. © 2007 Wiley‐Liss, Inc.

The hypermethylation of the O6‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation

“…Losses from chromosome 10 have been shown to be a negative prognostic factor in high-grade astrocytomas (Balesaria et al, 1999;Tada et al, 2001;Ohgaki et al, 2004) and in oligodendroglial tumors (Thiessen et al, 2003;Trost et al, 2007). In this study, the minimal common overlapping area in 10q26.13-26.2 was lost in 71.4% of glioblastomas.…”

Loss of CIC and FUBP1 expressions are potential markers of shorter time to recurrence in oligodendroglial tumors

“…Genetic alterations such as EGFR amplification, 7p gain and 21q loss have been associated with shorter survival. 27,28 Tumors carrying 1p/19q codeletion are correlated with IDH mutation, proneural gene expression pattern and a hypermethylated phenotype CIMP þ and are linked to favorable prognosis. [29][30][31] However, a fraction of patients with 1p/19q codeletion exhibit poor survival, despite combined radiochemotherapy.…”

Oligodendrogliomas: Molecular Biology and Treatment

“…In an intriguing study on 70 patients with grade II and III oligodendroglial tumors, a number of prognostically unfavorable genomic alterations were identified, in particular, gain of 7p and 8q and loss of 9p, 10q, and 18q [36]. In the anaplastic tumors, the presence of the 1p/19q codeletion was a favorable prognostic factor, particularly if no other unfavorable genomic aberrations had been identified.…”