Combined expression analysis and SNP-based measurement of copy number variation in ovarian cancer.

对于患有晚期卵巢癌的女性来说，她对铂类药物的反应程度和持续时间可能是她长期存活的唯一最重要的决定因素。目前，我们无法准确预测这种反应，尽管付出了巨大的努力，我们也不知道是什么因素控制了她对治疗的最初反应，以及几乎不可避免的铂难治疾病的复发。近年来，使用被称为微阵列的微型制造设备同时测量数千个基因的活动模式已经成为可能。由于异常的基因活性是肿瘤生长和药物敏感性的主要决定因素，我们预计这些信息将提供对肿瘤生长动态的洞察，并导致预测治疗反应和生存的测试。事实上，现在有许多实体癌症的例子，其中基于微阵列的表达信息可以预测结果，在乳腺癌中，这种信息正被积极地开发为临床工具。我们建议的研究是基于澳大利亚卵巢癌研究(AOCS)，这是一项通过美国国防部CDMRP-OCRP计划拨款于2003年1月建立的全国性研究。在仅仅24个多月的时间里，AOCs已经成为世界上同类研究中规模最大的，并为卵巢癌的分子分析提供了强大的生物资源。这项应用的目的是扩展AOCs浆液性卵巢癌病例的微阵列分析，特别是关注具有原发和获得性铂耐药的妇女。铂耐药是卵巢癌患者长期缓解的主要障碍。对大量精挑细选的病例进行高分辨率基因组分析，并与结果数据相关联，应该会为卵巢癌提供非常有价值的分子数据集。

For a woman with advanced ovarian cancer, the degree and duration of her response to platinum agents is probably the single most important determinant of her chance of survival for an extended period. At the moment we cannot accurately predict that response and, despite a great deal of effort, we don't understand what controls her initial response to treatment and almost inevitable relapse with platinum-refractory disease. In recent years it has become possible to measure the patterns of activity of thousands of genes simultaneously using microfabricated devices known as microarrays. As aberrant gene activity is a major determinant of tumour growth and drug sensitivity, we expect that such information will provide an insight into the dynamics of tumour growth and lead to tests that are predictive of treatment response and survival. Indeed, there are now a number of examples of solid cancers where microarray-based expression information is predictive of outcome and in breast cancer such information is being actively developed as a clinical tool. Our proposed research is based on the Australian Ovarian Cancer Study (AOCS), which is a national study established in January 2003 through a US Department of Defense CDMRP-OCRP Program grant. In just over 24 months AOCS has become the largest study of its kind in the world and represents a powerful bioresource for the molecular analysis of ovarian cancer. The objective of this application is to extend microarray analysis of AOCS serous ovarian cancer cases, particularly focusing on women with primary and acquired platinum resistance. Platinum resistance is the major barrier to long-term remissions in women with ovarian cancer. High-resolution genomic analysis of a large number of well-selected cases with linked outcome data should provide an extremely valuable molecular dataset for ovarian cancer.