Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization
Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization
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DOI：
10.1038/modpathol.3800607
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发表时间：
2006-06-01
期刊：
影响因子：
7.5
通讯作者：
Perlman, Elizabeth J.
中科院分区：
文献类型：
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作者：
Schneider, Dominik T.;Zahn, Susanne;Perlman, Elizabeth J.
迄今为止，有关中枢神经系统生殖细胞肿瘤遗传改变的信息有限，引起了人们对其与其他生殖细胞肿瘤实体的生物学关系的担忧。我们研究了 19 名中枢神经系统生殖细胞肿瘤 (CNS-GCT) 患者的新鲜冷冻或存档肿瘤样本，其中包括 7 例生殖细胞瘤、8 例恶性非生殖细胞瘤和 4 例畸胎瘤，使用染色体比较基因组杂交来确定复发性染色体失衡。所有 15 例恶性 CNS-GCT 和 4 例畸胎瘤中的 2 例均显示出多种染色体失衡。观察到染色体增益（中位数：4 个增益/肿瘤，范围：0-9 个增益/肿瘤）比缺失更频繁（中位数：1.6 个缺失/肿瘤，范围：0-6 个缺失/肿瘤）。 12p 的增加被认为是成人睾丸生殖细胞肿瘤的特征，在 19 个肿瘤中的 11 个和 15 个恶性 CNS-GCT 中的 10 个中检测到。在一个肿瘤中，12p 的增益仅限于 12p12 处的扩增子，对应于 12p 上常见的扩增区域。在染色体臂 1q 和 8q（各 n = 9）上发现了其他常见的增益。在染色体丢失中，11 号染色体 (n = 5)、18 号染色体 (n = 4) 和 13 号染色体 (n = 3) 的部分缺失最常见。值得注意的是，我们观察到生殖细胞和非生殖细胞 CNS-GCT 的基因谱没有差异；然而，后一组的平均失衡数量更高。一项比较 116 例恶性性腺和性腺外生殖细胞肿瘤的荟萃分析表明，CNS-GCT 中的基因组改变与相应年龄组的性腺或其他性腺外对应物中发现的基因组改变几乎没有区别。这些数据强烈支持性腺和性腺外生殖细胞肿瘤的常见发病机制。
The limited information available to date regarding the genetic alterations in germ cell tumors of the central nervous system has raised concerns about their biologic relationship to other germ cell tumor entities. We investigated fresh-frozen or archival tumor samples from 19 patients with central nervous system germ cell tumors (CNS-GCTs), including seven germinomas, eight malignant nongerminomatous germ cell tumors and four teratomas, using chromosomal comparative genomic hybridization to determine recurrent chromosomal imbalances. All 15 malignant CNS-GCTs and two of four teratomas showed multiple chromosomal imbalances. Chromosomal gains (median: 4 gains/tumor, range: 0-9 gains/tumor) were observed more frequently than losses (median: 1.6 losses/tumor, range: 0-6 losses/tumor). Gain of 12p, which is considered characteristic for germ cell tumors of the adult testis, was detected in 11 of 19 tumors and 10 of 15 malignant CNS-GCTs. In one tumor, gain of 12p was confined to an amplicon at 12p12, corresponding to the commonly amplified region on 12p. Other common gains were found on chromosome arms 1q and 8q (n = 9, each). Among the chromosomal losses, parts of chromosome 11 (n = 5), 18 (n = 4), and 13 (n = 3) were deleted most frequently. Notably, we observed no difference in the genetic profiles of germinomatous and nongerminomatous CNS-GCTs; however, the average number of imbalances was higher in the latter group. A meta-analysis comparing 116 malignant gonadal and extragonadal germ cell tumors revealed that the genomic alterations in CNS-GCTs are virtually indistinguishable from those found in their gonadal or other extragonadal counterparts of the corresponding age group. These data strongly argue in favor of common pathogenetic mechanisms in gonadal and extragonadal germ cell tumors.