Molecular Genetic Aspects of Oligodendrogliomas Including Analysis by Comparative Genomic Hybridization

Abstract

Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between molecular genetic parameters and histological pattern in this tumor type. Loss of heterozygosity (LOH) for 1p and 19q was seen in 17/23 (74%) well-differentiated oligodendrogliomas, in 18/23 (83%) anaplastic oligodendrogliomas, and in 3/8 (38%) oligoastrocytomas grades II and III. LOH for 17p and/or mutations of the TP53 gene occurred in 14 of these 55 tumors. Only one of the 14 cases with 17p LOH/TP53 gene mutation also had LOH for 1p and 19q, and significant astrocytic elements were seen histologically in the majority of these 14 tumors. LOH for 9p and/or deletion of the CDKN2A gene occurred in 15 of these 55 tumors, and 11 of these cases were among the 24 (42%) anaplastic oligodendrogliomas. Comparative genomic hybridization (CGH) identified the majority of cases with 1p and 19q loss and, in addition, showed frequent loss of chromosomes 4, 14, 15, and 18. These findings demonstrate that oligodendroglial neoplasms usually have loss of 1p and 19q whereas astrocytomas of the progressive type frequently contain mutations of the TP53 gene, and that 9p loss and CDKN2A deletions are associated with progression from well-differentiated to anaplastic oligodendrogliomas.

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

“…Other series of oligodendroglial tumors investigated by CGH previously yielded imbalances on these chromosomes at similar frequencies. 20,[30][31][32][33][34][35] With respect to the prognostic significance of genetic alterations, previous reports have mostly focussed on 1p/19q deletions, which were found to be significantly associated with longer survival of patients with oligodendroglial tumors. 10,12,[14][15][16][17]36 In line with these data, we found that combined 1p and 19q losses were associated with a better prognosis in our patients (increase in median patient survival of around 70 months, i.e.…”

Correlation of in vitro infiltration with glioma histological type in organotypic brain slices

“…Mixed OlAs were tumours in which the two cell populations with oligo-and astroglial phenotype were topographically separated, at least in some areas (Bigner et al, 1999); this definition basically corresponds to the biphasic OlAs in the WHO 2000 classification. Glioblastomas with oligodendroglial component (GOCs) (Bigner et al, 1999;Kleihues et al, 2002) were biphasic tumours with grade IV histological features.…”

Oligodendrogliomas: a short history of clinical developments

“…In an important next paper, Mainz et al showed that low-grade mixed oligoastrocytoma show either characteristic astrocytic lesions (TP53 mutations) or combined loss of 1p/19q, pointing out that at the molecular level mixed tumors do not exist [7]. Subsequent studies showed that anaplastic oligodendrogliomas showed in addition to 1p/19q loss other lesions (e.g., loss of 9p), but that typical genetic lesions found in glioblastoma were mutually exclusive with combined 1p/19q loss [8,9]. This pointed toward a glioblastoma-like genetic background of many anaplastic mixed oligoastrocytomas, further emphasizing that true mixed oligoastrocytic tumors do not exist.…”