Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about malignant progression detected using comparative genomic hybridization

Abstract

Object. Despite the rapid increase in knowledge concerning the genetic basis of malignant progression in astrocytic tumors, progression of oligodendroglial tumors (including both pure oligodendrogliomas and mixed oligoastrocytomas) is still poorly understood. The aim of the present study is the elucidation of chromosomal imbalances involved in the progression of oligodendroglial tumors toward malignancy. Methods. Using comparative genomic hybridization (CGH) on snap-frozen tumor tissue, the tumor genomes of five primary oligodendroglial tumors and associated recurrent tumors were screened for chromosomal imbalances. This information was correlated with clinical data (including follow-up data) and histopathological malignancy grade. In all cases an increase in chromosomal imbalances was detected in the recurrent tumor, indicating genetic progression. In three of the five cases this correlated with malignant progression detected at the histopathological level. The results indicate that, similar to what occurs in astrocytic tumors, chromosomal imbalances harboring genes involved in the cell proliferation control mechanism at the G1-S border are involved in the progression of oligodendroglial tumors. Additionally, although gains of genetic material on chromosome 7 and losses on chromosome 10 are most frequently detected in the course of malignant progression of astrocytic tumors, either or both of these can also occur during malignant progression of typical oligodendroglial tumors that contain losses involving chromosome 1p and/or chromosome 19q. Conclusions. When performed on optimally preserved material from a small set of primary oligodendroglial tumors and associated recurrent tumors, CGH detects chromosomal aberrations that potentially play a mechanistic role in the malignant progression of these tumors.