Gene Copy Number Changes and Breast Cancer Survival

描述（由申请人提供）：本研究基于以下假设：内源性和外源性因素可导致易感乳腺上皮细胞基因组结构变化的产生或选择，这些变化反过来影响乳腺癌的表型和行为。该项目汇集了一个在基因组学、病理学、流行病学、生物统计学和临床研究方面技能娴熟的跨学科团队：1)利用阵列CGH分析大量纯化乳腺肿瘤样本，确定遗传物质的频繁损失和获得；2)确定拷贝数变化的特定区域与特定患者和肿瘤属性之间的关系。鉴别乳腺肿瘤中与种族、危险因素、肿瘤特征和乳腺癌生存相关的染色体改变区域是了解非裔美国人和白人妇女乳腺癌潜在生物学和临床行为的重要一步。为了明确实现我们的总体目标，我们将：1)使用基于阵列的CGH方法来识别398名女性（307名白种人和91名非裔美国人）肿瘤中频繁扩增和/或缺失的染色体区域；2)检查遗传变化、种族、危险因素、患者特征和乳腺癌生存之间的关系；3)使用高分辨率阵列来完善与危险因素或生存相关的候选区域。

DESCRIPTION (provided by applicant): This study is predicated on the hypotheses that endogenous and exogenous factors can lead to the production or selection of genomic structural changes in susceptible breast epithelial cells and that these changes in turn affect phenotype and behavior of breast cancers. This project brings together an interdisciplinary team skilled in genomics, pathology, epidemiology, biostatistics and clinical research to: 1) identify frequent losses and gains of genetic material using array CGH analysis on a large set of purified breast tumor samples and 2) determine the relationship between specific regions of copy number change and particular patient and tumor attributes. The identification of altered chromosomal regions in breast tumors in relation to race, risk factors, tumor characteristics and breast cancer survival is an important step toward understanding the underlying biology and clinical behavior of the disease in African American and white women. To specifically address our overall goals, we will: 1) use array-based CGH methods to identify chromosomal regions that show frequent amplification and/or deletion in tumors of 398 women (307 Caucasian and 91 African American), 2) examine the association between genetic changes race, risk factors, patient characteristics and breast cancer survival, and 3) use high-resolution arrays to refine candidate regions that are associated with risk factors or survival.