Hirose Yuichi, Aldape Kenneth D, Chang Susan, Lamborn Kathleen, Berger Mitchel S, Feuerstein Burt G
Department of Neurological Surgery, University of California, San Francisco, CA 94115, USA.
Cancer Genet Cytogenet. 2003 Apr 1;142(1):1-7. doi: 10.1016/s0165-4608(02)00791-4.
Grade II astrocytoma is defined as a low-grade tumor, yet patients have a wide range of survival and tumors can quickly progress to high-grade astrocytoma/glioblastoma. Previous studies using comparative genomic hybridization (CGH) failed to demonstrate frequent copy number aberrations (CNA) in these tumors. This may be related to technical difficulties because infiltrating astrocytic tumors are often intermixed with normal brain tissue. We developed methods to exclude most normal tissue and use small amounts of DNA for CGH by microdissecting small regions of tumor from paraffin sections and amplifying extracted DNA using degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Using this method, we examined 30 grade II astrocytoma cases. We found CNA in 25 cases (83%), with a mean of two CNA per case. The most frequent CNA were gains on 7q (12 cases), 5p (5 cases), 9 (5 cases), and 19p (3 cases), and losses on 19q (7 cases), 1p (6 cases), and Xp (3 cases). Gain on 7q and losses on 1p/19q were mutually exclusive. This is the first report on the genetic characterization of low-grade astrocytomas using CGH from microdissected and formalin-fixed tissue. The comparatively large number of cases in this study allows us to suggest that these tumors are genetically subgrouped.
二级星形细胞瘤被定义为低级别肿瘤,但患者的生存期差异很大,且肿瘤可迅速进展为高级别星形细胞瘤/胶质母细胞瘤。以往使用比较基因组杂交(CGH)的研究未能在这些肿瘤中发现频繁的拷贝数畸变(CNA)。这可能与技术困难有关,因为浸润性星形细胞肿瘤常与正常脑组织混合在一起。我们开发了一些方法,通过从石蜡切片中显微切割肿瘤的小区域并使用简并寡核苷酸引物聚合酶链反应(DOP-PCR)扩增提取的DNA,来排除大部分正常组织并使用少量DNA进行CGH。使用这种方法,我们检查了30例二级星形细胞瘤病例。我们在25例(83%)中发现了CNA,平均每例有两个CNA。最常见的CNA是7q(12例)、5p(5例)、9(5例)和19p(3例)的增益,以及19q(7例)、1p(6例)和Xp(3例)的缺失。7q增益和1p/19q缺失相互排斥。这是第一篇关于使用来自显微切割和福尔马林固定组织的CGH对低级别星形细胞瘤进行基因特征分析的报告。本研究中相对大量的病例使我们能够提出这些肿瘤在基因上是可分组的。