Minimum Regions of Genomic Imbalance in Stage I Testicular Embryonal Carcinoma and Association of 22q Loss with Relapse
Minimum Regions of Genomic Imbalance in Stage I Testicular Embryonal Carcinoma and Association of 22q Loss with Relapse
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DOI：
10.1002/gcc.20843
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发表时间：
2011-03-01
影响因子：
3.7
通讯作者：
Shipley, Janet
中科院分区：
文献类型：
--
作者：
Gilbert, Duncan C.;McIntyre, Alan;Shipley, Janet
睾丸生殖细胞肿瘤（TGCT）是影响年轻成年男性最常见的实体瘤，在组织学上分为精原细胞瘤和非精原细胞瘤（NS）。 NS包括未分化胚胎癌（EC）和具有胚胎（畸胎瘤）或胚胎外（绒毛膜癌、卵黄囊肿瘤）特征的分化肿瘤。与其他亚型相比，EC 具有均一的细胞形态并且缺乏正常细胞浸润，非常适合核酸分析。由于 EC 相对罕见，因此在之前的研究中代表性不足。为了深入了解 NS 肿瘤发生、转移扩散和潜在的复发标志物，使用完整平铺路径 BAC 平台从来自患者的 32 个福尔马林固定石蜡包埋的 1 期 EC 样本中获取阵列比较基因组杂交 (aCGH) 谱，并提供后续数据。除了识别先前在 TGCT 中描述的区域外，还通过荧光原位杂交分析定义并确认了 6p21.33、10q11.21 和 22q13.32 处的增益以及 22q12.2 处的丢失的新最小重叠区域。具体来说，6p21.33 的区域包括 OCT3/4，其表达参与多能性的维持，而 10q11.21 区域包含编码 RAS 激活因子 RASGEF1A 的基因，从这些样品中提取的 RNA 中，该基因的表达明显增加。 22q12.2 的缺失区域在复发的肿瘤中更为常见，并且 22q12.2 的基因蛋白表达（包括 PIK3IP1）（PI3 激酶信号传导的负调节因子）降低。这些数据支持了参与多能性和 RAS/PI3K 信号传导的基因在 EC 发育和进展中的作用。 (C) 2010 Wiley-Liss, Inc.
Testicular germ cell tumors (TGCT) are the most frequent solid tumor to affect young adult males and are histologically divided into seminomas and nonseminomas (NS). NS comprise undifferentiated embryonal carcinoma (EC) and differentiated tumors with embryonic (teratoma) or extra-embryonic (choriocarcinoma, yolk sac tumor) features. In contrast to other subtypes, EC have uniform cellular morphology and lack normal cell infiltrates, ideal for nucleic acid profiling. EC are under-represented in previous studies due to their relative rarity. To gain insights into NS tumorigenesis, metastatic dissemination and potential markers of relapse, a full tiling path BAC platform was used to obtain array comparative genomic hybridization (aCGH) profiles from 32 formalin fixed paraffin embedded stage 1 EC samples from patients with follow-up data. In addition to identifying regions previously described in TGCT, novel minimum overlapping regions of gain at 6p21.33, 10q11.21, and 22q13.32 and loss at 22q12.2 were defined and confirmed by fluorescence in situ hybridization analyses. Specifically, the region at 6p21.33 included OCT3/4, the expression of which is involved in the maintenance of pluripotency and the 10q11.21 region contains the gene encoding the RAS activating factor RASGEF1A, the expression of which was demonstrably increased in RNA extracted from these samples. The region of loss at 22q12.2 was more frequently seen in tumors that relapsed and protein expression of genes from 22q12.2 included PIK3IP1, a negative regulator of PI3 kinase signaling was reduced. These data support the role for genes involved in pluripotency and RAS/PI3K signaling in EC development and progression. (C) 2010 Wiley-Liss, Inc.