Molecular genetic alterations in glioblastomas with oligodendroglial component

Abstract.

Glioblastoma multiforme is the most malignant astrocytic glioma and usually resistant to chemotherapy. A small fraction of glioblastomas may contain areas with histological features of oligodendroglial differentiation. To determine the molecular genetic alterations in such "glioblastomas with oligodendroglial component", we investigated 13 of these tumors for genetic alterations and/or expression of the TP53, CDKN2A, PTEN, and EGFR genes. In addition, we performed microsatellite analyses for loss of heterozygosity (LOH) on chromosome arms 1p, 19q and 10q. None of tumors showed evidence for LOH on 10q. LOH on 1p was detected in 3 tumors, 1 of which additionally showed 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 identified in 3 of these cases. Further aberrations detected were epidermal growth factor receptor (EGFR) overexpression (3 of 13 tumors), homozygous CDKN2A deletion (2 of 11 tumors), and PTEN mutation (1 of 13 tumors). Taken together, our results indicate that "glioblastomas with oligodendroglial component" carry heterogeneous genetic alterations. LOH on 10q, PTEN mutation, and homozygous CDKN2A deletion appear to be less common in these tumors as compared to ordinary glioblastomas. Furthermore, a subset of these tumors demonstrates LOH on 1p, i.e., an alteration that has recently been linked to chemosensitivity and good prognosis in anaplastic oligodendrogliomas.