Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1
Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1
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DOI：
10.1038/sj.onc.1206302
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发表时间：
2003-03-27
期刊：
影响因子：
8
通讯作者：
Shipley, JM
中科院分区：
文献类型：
--
作者：
Rodriguez, S;Jafer, O;Shipley, JM
12 p物质的获得总是与青少年和成人的睾丸生殖细胞肿瘤（TGCT）相关，最常见的是等染色体12 p。我们使用针对染色体的表达谱的全局方法（比较表达序列杂交，CESH）分析了具有i（12 p）的TGCT。这表明相对于睾丸组织和成纤维细胞，12p11.2-p12.1的基因过表达。非腺瘤亚型的表达水平高于腺瘤。值得注意的是，12p11.2-p12.1在约10%的TGCT中扩增，并且这种扩增子病例的CESH分析显示来自该区域的高水平过表达。将微阵列分析（包括代表来自12p11.2-p12.1的大多数UniGene簇的cDNA克隆）应用于来自扩增12p11.2-p12.1的5个TGCT和获得12号染色体的整个短臂的7个TGCT的DNA和RNA。表达谱与CESH数据一致，在大多数TGCT中检测到EST 595078、MRPS 35和LDHB在12p11.2-p12.1的过表达。BCAT 1的高水平过表达是非胶质瘤特异性的，CMAS、EKI 1、KRAS 2、SURB 7和各种ESTs等基因的过表达与其扩增相关。12 p13的CCND 2、GLU 3、LRP 6和HPH 1等基因也过表达。鉴定的过表达序列，特别是扩增区域中的那些，代表参与TGCT发展的候选基因。
Gain of 12p material is invariably associated with testicular germ cell tumors (TGCTs) of adolescents and adults, most usually as an isochromosome 12p. We analyzed TGCTs with i(12p) using a global approach to expression profiling targeting chromosomes (comparative expressed sequence hybridization, CESH). This indicated overexpression of genes from 12p11.2-p12.1 relative to testis tissue and fibroblasts. The nonseminoma subtype showed higher levels of expression than seminomas. Notably, 12p11.2-p12.1 is amplified in about 10% of TGCTs and CESH analysis of such amplicon cases showed high levels of overexpression from this region. Microarray analysis, including cDNA clones representing most UniGene clusters from 12p11.2-p12.1, was applied to DNA and RNA from 5 TGCTs with amplification of 12p11.2-p12.1 and seven TGCTs with gain of the entire short arm of chromosome 12. Expression profiles were consistent with the CESH data and overexpression of EST595078, MRPS35 and LDHB at 12p11.2-p12.1 was detected in most TGCTs. High-level overexpression of BCAT1 was specific to nonseminomas and overexpression of genes such as CMAS, EKI1, KRAS2, SURB7 and various ESTs correlated with their amplification. Genes such as CCND2, GLU3, LRP6 and HPH1 at 12p13 were also overexpressed. The overexpressed sequences identified, particularly those in the region amplified, represent candidate genes for involvement in TGCT development.