Genetic Signature of Oligoastrocytomas Correlates with Tumor Location and Denotes Distinct Molecular Subsets

Abstract

Oligoastrocytomas are heterogeneous tumors that have molecular features that overlap with either oligodendrogliomas or astrocytomas. Differences in the frequency of chromosomal losses of 1p and 19q in oligodendrogliomas are related to tumor location, with a low rate of allelic loss in tumors of the temporal and a high rate in tumors of the frontal, parietal, and occipital lobes. To test the possibility of regional molecular heterogeneity in oligoastrocytoma, we examined a series of 203 gliomas including 68 oligoastrocytomas and two control groups of 73 oligodendrogliomas and 62 astrocytomas for allelic losses of chromosomal arms 1p and 19q, and TP53 mutations, and compared these data with tumor localization. Common molecular alterations were found in oligodendrogliomas and oligoastrocytomas arising in extratemporal sites. In respect to the molecular parameters analyzed, temporal oligoastrocytomas were either indistinguishable from astrocytoma or similar to temporal oligodendrogliomas. Oligodendroglial neoplasms can thus be separated into three molecular subsets, two of which include lesions with the morphological features of oligodendrogliomas and oligoastrocytomas and one resembling temporal oligoastrocytoma. Molecular subclassification thus unifies previous findings about prognosis, behavior, response Oligodendroglial tumors, including oligodendrogliomas and oligoastrocytomas, constitute between 5% and 18% of all primary human brain tumors.1-4 Advances in diagnostic recognition and clinical management have succeeded in a dramatic improvement of the clinical outcome of patients with anaplastic oligodendroglioma. Distinct molecular subsets of oligodendroglial tumors also have highly differential responses to therapy. 5,6 Therefore, the further identification and evaluation of diagnostic parameters with high prognostic power is of great interest in oligodendroglial neoplasms.Somatic deletions on the short arm of chromosome 1 [loss of heterozygosity (LOH) 1p] and the long arm of chromosome 19 (LOH 19q) are typical of oligodendroglioma and oligoastrocytoma. [7][8][9][10][11][12] To date, however, neither the 1p nor 19q gene has been identified. Although LOH 19p is also frequently seen in anaplastic astrocytomas and may be associated with tumor progression, LOH 1p is more closely associated with oligodendroglial gliomas. 13 The combination of LOH 1p and LOH 19q is observed only rarely in gliomas other than oligodendroglioma and oligoastrocytoma. 11Oligoastrocytomas exhibit both astrocytic and oligodendroglial morphologies.14 Because of the rather vague criteria for defining oligoastrocytoma, the incidence of oligoastrocytoma varies considerably between different studies. Based on molecular findings, oligoastrocytomas occupy an intermediate position between oligodendrogliomas and astrocytomas. From 30 to 70% of oligoastrocytomas show LOH 1p and LOH 19q 8 -12,15 thus genetically resembling oligodendrogliomas, whereas ϳ30% show mutations in the TP53 gene or LOH 17p 10,16 suggesting a relation to astrocytomas. Signific...

Simulation of anisotropic growth of low‐grade gliomas using diffusion tensor imaging

“…Thus, it should be possible to use this model to determine the starting location of the tumor. This is important because it is believed that tumor location correlates with other characteristics, such as the genetic molecular profile (27,28). …”

Pdgfr‐α in 1p/19q LOH oligodendrogliomas

“…This LOH 1p/19q distribution pattern is similar to results previously reported in oligodendrogliomas. 8,10 Proteins from these 28 oligodendrogliomas (13 WHO grade II and 15 WHO grade III) were denatured, separated by electrophoresis Figure 1.…”

Correlation of histomorphologic prognostic markers and proliferative index with loss of heterozygosity 1p/19q and MGMT status in diffusely infiltrating gliomas

“…2,7,8 It is also an indicator of better OS and enhanced chemosensitivity. 1,8,9 However, its utility in astrocytic tumours remains largely unexplored.…”