【摘要】 目的研究髓母细胞瘤全基因组的遗传学异常,探讨癌基因的异常表达在髓母细胞瘤发病机制中的作用以及与预后的关系。方法应用比较基因组杂交(comparativegenomichybridization,CGH)技术检测14例髓母细胞瘤全基因组的遗传学改变;同时,在扩大系列的29例髓母细胞瘤中,应用荧光原位杂交(fluorescenceinsituhybridization,FISH)和免疫组化染色分别检测ERBB2在基因水平和蛋白水平的表达。结果(1)CGH结果显示,在所有14例髓母细胞瘤标本中,每一条染色体臂上都检测到了染色体的失衡(获得或丢失),最常见的染色体异常为17q(85.7%)和7q(35.7%)的获得,以及8p(50%)、16q(28.6%)和17p(35.7%)的丢失;(2)FISH检测中,44.5%(13/29例)的肿瘤细胞有ERBB2基因的异常表达;(3)免疫组化结果显示,37.9%(11/29例)的病例有抗体cerbB2的阳性表达;(4)在预后较差的16例患者中,56%(9/16例)的病例有ERBB2的过度表达。结论CGH研究发现了髓母细胞瘤全基因组的染色体失衡。在染色体17q特异性位点上ERBB2基因的异常改变很可能在髓母细胞瘤的发病机制中起着重要的作用,其过度表达与患者的预后密切相关。更多还原

【Abstract】 Purpose To detect genetic alterations across the entire genome in medulloblastoma, and to study the relationship between the expression of oncogene and the pathogenesis of medulloblastoma, as well as the prognosis of the tumor patients. Methods Comparative genomic hybridization (CGH) analysis was performed in 14 cases of medulloblastomas. In an extensive series of 29 medulloblastomas, the expression of ERBB-2 was studied by using fluorescence in situ hybridization (FISH) and immnunohistochemical analyses. Results (1) Genetic imbalances (DNA gain or loss) were detected on at least one chromosomal arm in all 14 cases. The most common chromosomal alterations were gains on 17q (85.7%) and 7q (35.7%), as well as losses on 8p (50%), 16q (28.6%) and 17p (35.7%). (2) Overexpression of ERBB-2 were demonstrated in 44.5% (13/29 cases) by FISH analysis. (3) Immunohistochemically,37.9% (11/29 cases) samples revealed c-erbB-2 positive reaction. (4) Overexpression of ERBB-2 was detected in 56% (9/16 cases) of patients with poor outcome. Conclusions CGH analysis demonstrates genome-wide chromosomal imbalances in medulloblastoma. The alteration of ERBB-2 gene on the specific region of chromosome 17q may play an important role in the pathogenesis of medulloblastoma. Moreover, overexpression of ERBB-2 is closely associated with the poor prognosis of medulloblastoma patients.更多还原