gms | German Medical Science

Objective: In contrast to astrocytic tumors including glioblastomas (GBM), oligodendrogliomas (O) have a better prognosis and increased responsiveness to chemotherapy. Interestingly, a small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation. In the current WHO classification (2007) these tumors are now included as a variant of glioblastomas and are called glioblastomas with oligodendroglial component (GBMO). However, definitive diagnostic criteria still do not exist.

Methods: We used a genome wide approach (chromosomal comparative genomic hybridization (CGH) and molecular karyotyping) in combination with interphase fluorescence in situ hybridization (FISH) (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) to genetically characterize GBMO and “classical” O. We analyzed the oligodendroglial and the astrocytic glioblastoma parts of 13 GBMO separately by chromosomal CGH of microdissected paraffin embedded tumor tissue and interphase FISH on paraffin sections. Furthermore, freshly frozen material of eight oligodendrogliomas (3 WHO grade II, 5 WHO-grade III) and two oligoastrocytomas (OA) WHO grade II was examined genome wide by using the standard Agilent 244A chip.

Results: Four distinct genetic subtypes in GBMO were identified: an “astrocytic” subtype (9/13) characterized by +7/-10; an “oligodendroglial” subtype with -1p/-19q (1/13); an “intermediate” subtype showing +7/-1p (1/13), and an “other” subtype having none of the former aberrations typical for gliomas (2/13). In contrast, most “classical” O (7/8) and one of two OA showed combined 1p/19q deletion, corresponding genetically to the “oligodendroglial” subtype. Five of the O with 1p/19q codeletion showed additional aberrations (e. g. –4, –14, –9, –18). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for their oligodendroglial and astrocytic parts. These findings demonstrate the monoclonal origin of the tumor followed by the formation of the astrocytic and oligodendroglial components. We are currently evaluating the array CGH results of the oligodendrogliomas, which will also be presented.

Conclusions: The diagnostic determination of these genetic signatures might be of prognostic value for those patients. Our results underline the importance of molecular cytogenetic analyses to supplement the histological diagnosis of gliomas.