Molecular genetic alterations in glioblastomas with oligodendroglial component

Glioblastoma multiforme is the most malignant astrocytic glioma and usually resistant to chemotherapy. A small fraction of glioblastomas may contain a reas with histological features of oligodendroglial differentiation. To det ermine the molecular genetic alterations in such ,,glioblastomas with oligo dendroglial component", we investigated 13 of these tumors for genetic alte rations and/or expression of the TP53, CDKN2A, PTEN, and EGFR genes. In add ition, we performed microsatellite analyses for loss of heterozygosity (LOH ) on chromosome arms 1p, 19q and 10q. None of tumors showed evidence for LO H on 10q. LOH on 1p was detected in 3 tumors, 1 of which additionally showe d LOH on 19q. The 3 tumors with LOH on 1p showed neither TP53 mutations nor nuclear p53 accumulation. In contrast, 9 of 10 tumors without demonstrated losses on 1p showed nuclear p53 accumulation. TP53 mutations were identifi ed in 3 of these cases. Further aberrations detected were epidermal growth factor receptor (EGFR) overexpression (3 of 13 tumors), homozygous CDKN2A d eletion (2 of 11 tumors), and PTEN mutation (1 of 13 tumors). Taken togethe r, our results indicate that "glioblastomas with oligodendroglial component " carry heterogeneous genetic alterations. LOH on 10q, PTEN mutation, and h omozygous CDKN2A deletion appear to be less common in these tumors as compa red to ordinary glioblastomas. Furthermore, a subset of these tumors demons trates LOH on 1p, i.e., an alteration that has recently been linked to chem osensitivity and good prognosis in anaplastic oligodendrogliomas.