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12p-Amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH

机译：12P-扩增子结构分析青少年睾丸生殖细胞瘤和成人阵列CGH

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All invasive testicular germ cell tumors of adolescents and adults (TGCTs), that is, seminomas and nonseminomas, show gain of 12p sequences, mostly as isochromosomes. Although several candidate genes have been suggested, the relevant gene(s) have not been identified yet. About 10% of testicular seminomas, however, show a more restricted amplification of the 12p11.2–p12.1 region, in which the various amplicons show an apparent overlap, allowing for the shortest region of amplification overlap approach, aiming at the identification of pathogenetically relevant sequences residing in this region. Here we report on a high-resolution 12p-amplicon architecture analysis using microarray-based comparative genomic hybridization, the results of which were subsequently confirmed by fluorescent in situ hybridization studies. The 12p-specific microarray contained 63 positionally selected BAC clones, which are more or less evenly distributed over the short arm of chromosome 12 (average spacing: less than 500Kb), including 20 clones within the region of amplification. Out of a series of 17 seminomas, seven seminomas showed amplification of the whole amplicon region, of which three showed a dip in T/R value in the center of the amplified area. A more complex amplification pattern was found in the other 10 seminomas: three showed predominant amplification at the centromeric border; one mainly at the telomeric border; six showed a balanced amplification of both the centromeric and telomeric regions. The only nonseminoma investigated showed a structure in which the centromeric border was only amplified. These data support a mechanistic model in which at least two 12p genes, situated at the border regions of the amplicon, are positional candidates capable of actively supporting tumor progression in TGCTs.
机译：所有侵入性睾丸生殖细胞瘤的青少年和成人（TGCTS），即emminomas和非eminomas，显示12P序列的增益，大多为等色素。虽然已经提出了几种候选基因，但尚未确定相关基因。然而，大约10 ％的睾丸校验次数显示了12P11.2-P12.1区域的更受限制的放大器，其中各种扩增子显示出表观重叠，允许最短的放大重叠方法，旨在识别居住在该地区的病原质相关序列。在这里，我们通过基于微阵列的比较基因组杂交报告了高分辨率12P-扩增子架构分析，其结果随后通过荧光杂交研究证实。 12P特异性微阵列含有63个位置选择的BAC克隆，其在染色体12的短臂上或多或少地分布在染色体12的短臂上（平均间隔：小于500kb），包括扩增区域内的20个克隆。在17个校验组中，七个校验型显示出整个扩增子区域的放大，其中三个在放大区域的中心显示了T / R值的倾角。在其他10个校验中发现了一种更复杂的扩增模式：三个在焦化边界处显示出优势扩增;一个主要在极端边界;六显示了焦化和端粒区域的平衡扩增。研究的唯一的非狂犬瘤显示出一种仅扩增焦化边界的结构。这些数据支持机械模型，其中至少两个位于扩增子的边界区域的12P基因，是能够主动支持TGCT的肿瘤进展的位置候选。

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