Biospecimen: Genomics and Pathology

非洲血统(AA)女性比欧洲血统(EA)女性更有可能成为 在45岁之前被诊断为乳腺癌，并有更多侵袭性的肿瘤，染色为阴性 雌激素和孕激素受体和HER-2(三阴性)。它们也更有可能有类基底细胞 乳腺肿瘤是一种预后较差的固有乳腺癌亚型。造成这些差距的原因 都不清楚。我们建议将4个最大的乳房研究的样本、数据和专业知识结合起来 AA妇女的癌症以阐明早发性侵袭性乳腺癌的危险因素。初级阶段 本P01中4个项目中每个项目的因变量都是乳腺癌亚型，特别强调 在基底样瘤上。因此，这个核心的一个主要目的是协调肿瘤块的收集和 构建组织微阵列(TMA)。肿瘤块将在CBCS、BWHS和WCHS收集。 将进行免疫组织化学以确定乳腺癌亚型，幻灯片由两人阅读 独立的病理学家。关于MEC患者亚型的数据将被独立评估和发送 生物统计和数据管理核心。CORE C将对所有4个项目进行基因分型。《核心》 将协调所有4个国家的DNA提取、全基因组扩增、量化和平板化 研究，并使用为llLumina GoldGate平台开发的3个Opas进行基因分型核心还将 对基底样和腔性A病例的子集进行DNA重测序以识别用于精细定位的新SNPs 发现罕见的易感等位基因。进一步协助绘制精细地图，并查明与全球气候变化相关的 项目1、新鲜冷冻的基底样瘤和腔A瘤中基底样瘤和腔A瘤的表达特征 乳腺肿瘤将使用安捷伦244K微阵列进行基因表达分析。核心C也将 为项目研究人员提供与肿瘤病理学和基因组学有关的咨询。《核心》 领导者将与项目绩效指标合作，提供乳腺癌病理和肿瘤亚型方面的专业知识， 设计OPA，执行质量控制并协助数据解释。一个在线学习数据库， 存档的染色肿瘤切片的数字图像和基因簇数据将有助于及时获得数据 分析。所有生物检疫的一致和严格的处理和处理将确保 P01合作的完整性。

Women of African ancestry (AA) women are more likely than those with European ancestry (EA) to be diagnosed with breast cancer before age 45, and to have more aggressive tumors, with negative staining for estrogen and progesterone receptors and HER-2 (triple negative). They are also more likely to have basal-like breast tumors, an intrinsic breast cancer subtype with poor prognosis. The reasons for these disparities are unclear. We propose to combine samples, data and expertise from 4 of the largest studies of breast cancer in AA women to elucidate risk factors for early-onset aggressive breast cancer. The primary dependent variable in each of the 4 Projects in this P01 is breast cancer subtype, with particular emphasis on basal-like tumors. Thus, a major purpose of this Core is to coordinate collection of tumor blocks and construction of tissue microarrays (TMAs). Tumor blocks will be collected in the CBCS, BWHS and WCHS. Immunohistochemistry will be performed for identification of breast cancer subtypes, with slides read by two independent pathologists. Data on subtypes of patients in the MEC will be independently evaluated and sent to the Biostatistics and Data Management Core. Core C will conduct genotyping for all 4 Projects. The Core will coordinate DNA extraction, whole genome amplification, quantification and plating of DNAs from all 4 studies, and genotyping using 3 OPAs developed for the lllumina GoldGate platform The Core will also resequence DNA from a subset of basal-like and luminal A cases to identify novel SNPs for fine-mapping and to discover rare susceptibility alleles. To further assist with fine-mapping and to identify GWAS-related expression signatures in basal-like and luminal A tumors for Project 1, fresh frozen basal-like and luminal A breast tumors will be assayed for gene expression using the Agilent 244K microarray. Core C will also provide consultation to Project investigators in matters related to tumor pathology and genomics. The Core leaders will work with Project PIs to provide expertise in breast cancer pathology and tumor subtyping, design OPAs, perform quality control and assist with data interpretation. An on-line study database with archived digital images of stained tumor sections and genotype cluster data will facilitate timely data analysis. The consistent and rigorous handling and processing of all biospecimens will guarantee the integrity of the P01 collaboration.