Sawiris G Peter, Sherman-Baust Cheryl A, Becker Kevin G, Cheadle Chris, Teichberg Diane, Morin Patrice J
Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Cancer Res. 2002 May 15;62(10):2923-8.
Ovarian cancer is a major cause of cancer death in women. Unfortunately, the molecular pathways underlying ovarian cancer progression are poorly understood, making the development of novel diagnostic and therapeutic strategies difficult. On the basis of our previous observations obtained from serial analysis of gene expression, we have constructed a specialized cDNA array for the study of ovarian cancer. Small, specialized arrays have several practical advantages and can reveal information that is lost in the "noise" generated by irrelevant genes present in larger arrays. The array, which we named Ovachip, contains 516 cDNAs chosen from our serial analysis of gene expression and cDNA array studies for their relevance to ovarian cancer. The gene expression patterns revealed with the Ovachip are highly reproducible and extremely consistent among the different ovarian specimens tested. This array was extremely sensitive at differentiating ovarian cancer from colon cancer based on expression profiles. The Ovachip revealed clusters of coordinately expressed genes in ovarian cancer. One such cluster, the IGF2 cluster, is particularly striking and includes the insulin-like growth factor II, the cisplatin resistance-associated protein, the checkpoint suppressor 1, the cyclin-dependent kinase 6, and a protein tyrosine phosphatase receptor. We also identified a cluster of down-regulated genes that included the cyclin-dependent kinase 7 and cyclin H. Thus, the Ovachip allowed us to identify previously unidentified clusters of differentially expressed genes that may provide new paradigms for molecular pathways important in ovarian malignancies. Because of the relevance of the arrayed genes, the Ovachip may become a powerful tool for investigators in the field of ovarian cancer and may facilitate progress in understanding the etiology of this disease and in its clinical management.
卵巢癌是女性癌症死亡的主要原因。遗憾的是，人们对卵巢癌进展背后的分子途径了解甚少，这使得新型诊断和治疗策略的开发变得困难。基于我们先前通过基因表达序列分析获得的观察结果，我们构建了一个专门用于研究卵巢癌的cDNA阵列。小型专门阵列具有几个实际优势，并且可以揭示在大型阵列中无关基因产生的“噪音”中丢失的信息。我们将该阵列命名为Ovachip，它包含从我们的基因表达序列分析和cDNA阵列研究中挑选出的516个与卵巢癌相关的cDNA。用Ovachip揭示的基因表达模式在不同测试的卵巢标本中具有高度可重复性且极其一致。基于表达谱，该阵列在区分卵巢癌和结肠癌方面极其敏感。Ovachip揭示了卵巢癌中协同表达基因的簇。其中一个这样的簇，即IGF2簇，特别引人注目，包括胰岛素样生长因子II、顺铂抗性相关蛋白、检查点抑制因子1、细胞周期蛋白依赖性激酶6和一种蛋白酪氨酸磷酸酶受体。我们还鉴定出了一个下调基因簇，其中包括细胞周期蛋白依赖性激酶7和细胞周期蛋白H。因此，Ovachip使我们能够鉴定出以前未识别的差异表达基因簇，这些基因簇可能为卵巢恶性肿瘤中重要的分子途径提供新的范例。由于阵列基因的相关性，Ovachip可能成为卵巢癌领域研究人员的有力工具，并可能促进在理解这种疾病的病因及其临床管理方面取得进展。
