Kraus J A, Lamszus K, Glesmann N, Beck M, Wolter M, Sabel M, Krex D, Klockgether T, Reifenberger G, Schlegel U
Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Acta Neuropathol. 2001 Apr;101(4):311-20. doi: 10.1007/s004010000258.
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.
多形性胶质母细胞瘤是最恶性的星形胶质细胞瘤，通常对化疗耐药。一小部分胶质母细胞瘤可能包含具有少突胶质细胞分化组织学特征的区域。为了确定此类“具有少突胶质细胞成分的胶质母细胞瘤”中的分子遗传学改变，我们研究了其中13例肿瘤的TP53、CDKN2A、PTEN和EGFR基因的遗传学改变和/或表达情况。此外，我们对1号、19号和10号染色体臂上的杂合性缺失（LOH）进行了微卫星分析。所有肿瘤均未显示10号染色体臂上存在LOH。在3例肿瘤中检测到1号染色体臂上存在LOH，其中1例还显示19号染色体臂上存在LOH。1号染色体臂上存在LOH的3例肿瘤既未显示TP53突变，也未显示核p53积聚。相比之下，10例未显示1号染色体臂缺失的肿瘤中有9例显示核p53积聚。在其中3例中鉴定出TP53突变。检测到的其他异常包括表皮生长因子受体（EGFR）过表达（13例肿瘤中有3例）、CDKN2A纯合缺失（11例肿瘤中有2例）和PTEN突变（13例肿瘤中有1例）。综上所述，我们的结果表明“具有少突胶质细胞成分的胶质母细胞瘤”携带异质性遗传学改变。与普通胶质母细胞瘤相比，10号染色体臂上的LOH、PTEN突变和CDKN2A纯合缺失在这些肿瘤中似乎不太常见。此外，这些肿瘤的一个亚组显示1号染色体臂上存在LOH，即一种最近与间变性少突胶质细胞瘤的化疗敏感性和良好预后相关的改变。
