Genomic copy number and expression patterns in testicular germ cell tumours.

Genomic copy number and expression patterns in testicular germ cell tumours.
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DOI:
10.1038/sj.bjc.6604079
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发表时间:
2007-12-17
影响因子:
8.8
通讯作者:
Shipley, J.
Shipley, J.
中科院分区:
医学1区
文献类型:
--
作者:
McIntyre, A.;Summersgill, B.;Lu, Y. J.;Missiaglia, E.;Kitazawa, S.;Oosterhuis, J. W.;Looijenga, L. H.;Shipley, J.

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成人和青少年睾丸生殖细胞肿瘤(TGCT)包括精原细胞瘤(SE)和非精原细胞瘤(NS),其中精原细胞精原细胞瘤(SSE)是老年男性的一个独特实体。Se和NS在所有病例中都获得了12P物质,而SSE与9号染色体的过度表达有关。在这里,我们在染色体水平上比较了拷贝数失衡与全局表达变化,通过比较表达序列杂交分析,在7个SE、1个合并肿瘤、7个NS和7个细胞系中。尽管SE和NS的甲基化状态不同,但发现与拷贝数一致的正相关性是表达变化的主要驱动因素。对染色体拷贝数和表达数据的分析不能区分SE和NS,符合相似的遗传发病机制。然而,4q22、5q23.2和9p21的表达增加是SSE与SE和NS的区别,而2q36-q37和6q24的拷贝数和表达减少是NS来源的细胞系的特有特征。我们的分析还强调了超过40%的病例中存在拷贝数量和表达不平衡的19个区域。挖掘可用的表达阵列数据确定了这些区域的基因是参与TGCT开发的候选基因。有关补充数据,请访问http://www.crukdmf.icr.ac.uk/array/array.html.。
Testicular germ cell tumours of adults and adolescents (TGCT) include seminomas (SE) and nonseminomas (NS), with spermatocytic seminomas (SSE) representing a distinct entity in older men. SE and NS have gain of 12p material in all cases, whereas SSE are associated with overrepresentation of chromosome 9. Here, we compare at the chromosomal level, copy number imbalances with global expression changes, identified by comparative expressed sequence hybridisation analyses, in seven SE, one combined tumour, seven NS and seven cell lines. Positive correlations were found consistent with copy number as a main driver of expression change, despite reported differences in methylation status in SE and NS. Analysis of chromosomal copy number and expression data could not distinguish between SE and NS, in-keeping with a similar genetic pathogenesis. However, increased expression from 4q22, 5q23.2 and 9p21 distinguished SSE from SE and NS and decreased copy number and expression from 2q36–q37 and 6q24 was a specific feature of NS-derived cell lines. Our analysis also highlights 19 regions with both copy number and expression imbalances in greater than 40% of cases. Mining available expression array data identified genes from these regions as candidates for involvement in TGCT development. Supplementary data is available at http://www.crukdmf.icr.ac.uk/array/array.html.
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发表时间: 1991-01-01
影响因子: 45.3
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