Birch Ashley H, Quinn Michael C J, Filali-Mouhim Ali, Provencher Diane M, Mes-Masson Anne-Marie, Tonin Patricia N
Department of Human Genetics, McGill University, Montreal, Canada.
Mol Carcinog. 2008 Jan;47(1):56-65. doi: 10.1002/mc.20361.
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, RIS1 (at 3p21.31), 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.
细胞遗传学、分子遗传学和功能分析表明，3号染色体上的基因与上皮性卵巢癌（EOC）有关。为了进一步明确它们对EOC的作用，使用Affymetrix U133A基因芯片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）以及四种EOC细胞系（TOV-81D、TOV-112D、TOV-21G和OV-90）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进行的双向比较分析鉴定出278个差异表达基因，其中43个基因在至少50%的TOV样本中差异表达。三个基因，RIS1（位于3p21.31）、GBE1（位于3p12.2）和HEG1（位于3q21.2），在所有TOV样本中均同样低表达。这些基因表达失调与携带它们的基因座的杂合性缺失（LOH）无关。在一系列66例浆液性亚型恶性TOV样本中，RIS1、GBE1和HEG1基因座的LOH分析频率分别为14.3%、13.7%和9.2%。仅在致瘤性EOC细胞系（TOV-21G、TOV-112D和OV-90）中观察到RIS1、GBE1和HEG1表达水平降低，且与LOH无关。这些结果综合表明，与经典肿瘤抑制基因不同，RIS1、GBE1和HEG1不太可能是失活的主要靶点。本研究对NOSE和EOC样本中的3号染色体基因表达进行了全面分析，并鉴定出3号染色体上可供进一步研究的候选基因。
