Arslantas Ali, Artan Sevilhan, Oner Ulkü, Müslümanoğlu Hamza, Durmaz Ramazan, Cosan Erhan, Atasoy Metin Ant, Başaran Nurettin, Tel Eşref
Department of Neurosurgery, University of Osmangazi, Eskisehir, Turkey.
Neurosurg Rev. 2004 Jan;27(1):58-64. doi: 10.1007/s10143-003-0279-4. Epub 2003 Jul 4.
Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the progression of glioblastoma.
胶质肿瘤是神经系统最常见的肿瘤,可发生于任何年龄的个体。由于对人类胶质瘤潜在分子病理学的了解仍然非常有限,这种恶性肿瘤的治疗及预后尚未得到改善。为了确定不同的胶质母细胞瘤相关基因组畸变是否可与组织病理学结果相结合作为预后标志物,采用比较基因组杂交技术对20例原发性多形性胶质母细胞瘤进行筛查,并将结果与组织病理学和临床特征进行比较。所有肿瘤均显示通过比较基因组杂交检测到的基因组拷贝畸变。7号染色体拷贝数的区域增加和数目增加是最常见的异常(10/20例肿瘤),其次是10号染色体缺失(8/20)。这两种畸变均与较短的监测时间相关。在7例肿瘤中检测到12号染色体长臂扩增。在3例病例中发现17号染色体短臂、1号染色体和19号染色体长臂联合缺失。其中1例为巨细胞胶质母细胞瘤,而其余2例仍存活。在1例监测时间长的病例中也发现了1号染色体和19号染色体长臂联合缺失。根据本研究的初步结果,除表皮生长因子受体(EGFR)基因外,7号染色体上其他基因的扩增以及10号染色体上PTEN基因和其他癌症相关基因的缺失对多形性胶质母细胞瘤的发生似乎很重要,且与预后不良相关,而1号染色体和19号染色体长臂联合缺失似乎是预后较好的一个有意义的分子标志物。应通过大量病例比较原发性和继发性多形性胶质母细胞瘤的临床特征和基因改变,以明确有效的预后标志物;进一步针对7号和10号染色体的分子分析将有助于理解胶质母细胞瘤进展的分子机制。