Improving Breast Cancer Prognosis through Array CGH

通过阵列 CGH 改善乳腺癌预后

• 批准号: 6928953
• 负责人: Janet K. Bayleran
• 金额: $ 6.5万
• 依托单位: EASTERN MAINE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6928953
• 关键词: biotechnology; breast neoplasms; cancer risk; clinical research; comparative genomic hybridization; diagnosis quality /standard; early diagnosis; gene expression profiling; human genetic material tag; human subject; human therapy evaluation; loss of heterozygosity; microarray technology; molecular oncology; molecular pathology; neoplasm /cancer relapse /recurrence; polymerase chain reaction; prognosis; therapy design /development; biotechnology; breast neoplasms; cancer risk; clinical research; comparative genomic hybridization; diagnosis quality /standard; early diagnosis; gene expression profiling; human genetic material tag; human subject; human therapy evaluation; loss of heterozygosity; microarray technology; molecular oncology; molecular pathology; neoplasm /cancer relapse /recurrence; polymerase chain reaction; prognosis; therapy design /development

DESCRIPTION (provided by applicant): Millions of cancers are diagnosed every year in the United States. Cancer strikes more than 1/3rd of the population and accounts for more than 20% of all deaths. In addition, the economic burden of cancer is immense. Early diagnosis and treatment are vital and the identification of persons at increased risk of cancer is an important objective of cancer research. This application utilizes CGH microarray technology to [improve the detection and prognostic evaluation of breast cancer. An enhanced ability to predict the severity or aggressiveness of cancer will inevitably lead to improved interventional treatment.] The long-term objective of the research is to incorporate microarray technology into routine cancer protocols and to provide a comprehensive, multidisciplinary approach to cancer detection and treatment. The research involves paired comparison analyses of cancer patients on 2 levels. Firstly, it will compare microarray profiles of recently relapsed breast cancer patients at 2 points in time by analyzing DNA obtained from their current (flash-frozen) tumor and DNA obtained from their original (formalin-fixed, paraffin-embedded) tumor. Secondly, it will compare microarray profiles of the relapsed patients with profiles of DNA obtained from original tumors of matched patients who are still in remission during the same timeframe after initial diagnosis. Additional molecular analyses, such as Methylation-PCR and Loss of Heterozygosity testing will be performed to confirm and/or clarify microarray data. This project will take important steps towards the validation of CGH microarray technology for breast cancer detection and treatment. The aims of the project are predicated on the following hypotheses: [(1) that the profile of gene copy number abnormalities in breast carcinomas reflect its biological potential; (2) that genomic profiling has the ability to predict a subgroup of patients who are at greater risk for recurrence; and (3) that genomic profiles of breast cancer will help the clinician to provide individualized targeted therapy.] The ability to detect the [underlying molecular basis of breast cancer] and to provide sophisticated patient-specific monitoring of the efficacy of treatment is of manifest benefit to the entire U.S. population and also has broad relevance because of the incidence of breast cancer worldwide.

描述（由申请人提供）：美国每年都会诊断出数百万的癌症。癌症袭击超过人口的1/3，占所有死亡人数的20％以上。此外，癌症的经济负担巨大。早期诊断和治疗至关重要，鉴定患癌症风险的人是癌症研究的重要目标。该应用程序利用CGH微阵列技术来[改善对乳腺癌的检测和预后评估。提高预测癌症严重程度或侵略性的能力不可避免地会改善介入治疗。]研究的长期目标是将微阵列技术纳入常规癌症方案，并为癌症检测和治疗提供全面的多学科方法。该研究涉及在2个水平上对癌症患者的比较分析。首先，它将通过分析从其当前（闪 - 冻结）肿瘤获得的DNA和从其原始（福尔马林固定的，石蜡膜的）肿瘤获得的DNA来比较最近复发的乳腺癌患者的微阵列谱。其次，它将比较复发患者的微阵列特征，并从最初诊断后同一时间内仍处于缓解的匹配患者的原始肿瘤中获得的DNA谱。将进行其他分子分析，例如甲基化PCR和杂合性测试的丢失，以确认和/或澄清微阵列数据。该项目将采取重要步骤来验证CGH微阵列技术以进行乳腺癌检测和治疗。该项目的目的是基于以下假设：[（1）乳腺癌中基因拷贝数异常的特征反映了其生物学潜力； （2）基因组分析有能力预测重新发生风险更大的患者的亚组； （3）乳腺癌的基因组特征将有助于临床医生提供个性化的靶向治疗。]能够检测[乳腺癌的基本分子基础]并提供对治疗疗效的精致患者特异性监测的能力，这对整个美国人群具有明显的益处，并且由于乳腺癌的发生率广泛而具有广泛的相关性。