Transcriptome analysis of serous ovarian cancers identifies differentially expressed chromosome 3 genes
Transcriptome analysis of serous ovarian cancers identifies differentially expressed chromosome 3 genes
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DOI：
10.1002/mc.20361
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发表时间：
2008-01-01
影响因子：
4.6
通讯作者：
Tonin, Patricia N.
中科院分区：
文献类型：
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作者：
Birch, Ashley H.;Quinn, Michael C. J.;Tonin, Patricia N.
细胞遗传学、分子遗传学和功能分析表明3号染色体基因与上皮性卵巢癌（EOC）有关。为了进一步表征它们对EOC的贡献，使用Affytron U133 A基因芯片（（R））对正常卵巢表面上皮（NOSE）细胞（n = 14）、恶性浆液性上皮性卵巢肿瘤（TOV）（n = 17）和四种EOC细胞系（TOV-81 D、TOV-112 D、TOV-21 G和OV-90）的原代培养物中的3号染色体基因进行转录组分析。对735个已知基因和表达序列的双向比较分析鉴定了278个差异表达基因，其中43个基因在至少50%的TOV样品中差异表达。三个基因，R/S1（在3p21.31），GBE 1（在3p12.2），和HEG 1（在3q21.2），在所有TOV样品中类似地低表达。这些基因的表达失调与其所在基因座的杂合性丢失（洛）无关。在一系列66个浆液性亚型的恶性TOV样本中，观察到RIS 1、GBE 1和HEG 1位点的洛分析频率分别为14.3%、13.7%和9.2%。仅在致瘤性EOC细胞系（TOV-21 G、TOV-112 D和OV-90）中观察到RIS 1、GBE 1和HEG 1表达水平降低，且与洛无关。这些结果表明，与经典的肿瘤抑制基因不同，RIS 1，GBE 1和HEG 1不太可能是失活的主要靶点。这项研究提供了一个全面的分析3号染色体基因表达的NOSE和EOC样本，并确定3号染色体基因的候选人进行进一步研究。(c)2007 Wiley-Liss，Inc.
Cytogenetic, molecular genetic and functional analyses have implicated chromosome 3 genes in epithelial ovarian cancers (EOC). To further characterize their contribution to EOC, the Affymetrix U133A GeneChip((R)) was used to perform transcriptome analyses of chromosome 3 genes in primary cultures of normal ovarian surface epithelial (NOSE) cells (n = 14), malignant serous epithelial ovarian tumors (TOV) (n = 17), and four EOC cell lines (TOV-81D, TOV-112D, TOV-21G, and OV-90). A two-way comparative analysis of 735 known genes and expressed sequences identified 278 differentially expressed genes, where 43 genes were differentially expressed in at least 50% of the TOV samples. Three genes, R/S1 (at 3p2l.31), GBE1 (at 3p12.2), and HEG1 (at 3q21.2), were similarly underexpressed in all TOV samples. Deregulation of the expression of these genes was not associated with loss of heterozygosity (LOH) of the genetic loci harboring them. LOH analysis of the RIS1, GBE1, and HEG1 loci was observed at frequencies of 14.3%, 13.7%, and 9.2%, respectively, in a series of 66 malignant TOV samples of the serous subtype. Reduced expression levels of RIS1, GBE1, and HEG1 were observed only in the tumorigenic EOC cell lines (TOV-21G, TOV-112D, and OV-90) and did not correlate with LOH. These results combined suggest that RIS1, GBE1, and HEG1, unlike classical tumor suppressor genes, are not likely to be primary targets of inactivation. This study provides a comprehensive analysis of chromosome 3 gene expression in NOSE and in EOC samples and identifies chromosome 3 gene candidates for further study. (c) 2007 Wiley-Liss, Inc.