PROTEOGENOMIC ANALYSIS OF HUMAN-IN-MOUSE BREAST CANCER XENOGRAFTS

人鼠乳腺癌异种移植物的蛋白质组学分析

• 批准号: 8361435
• 负责人: MATTHEW J ELLIS
• 金额: $ 1.44万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361435
• 关键词: African American; Cells; DNA; DNA Sequence; Frequencies; Funding; Genome; Genomics; Grant; Human; Mass Spectrum Analysis; Metastatic malignant neoplasm to brain; Minority; Mus; Mutation; National Center for Research Resources; Neoplasm Metastasis; Patients; Pattern; Primary Neoplasm; Principal Investigator; Research; Research Infrastructure; Resources; Sampling; Source; Technology; United States National Institutes of Health; Variant; Xenograft procedure; biomedical resource; cost; malignant breast neoplasm; peripheral blood; tumor; tumor progression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 大规模并行DNA测序技术提供了一种前所未有的能力，可以筛选整个基因组中与肿瘤进展相关的遗传变化。在这里，我们描述了基因组分析的四个DNA样本的非裔美国人的基底样乳腺癌患者：外周血，原发性肿瘤，脑转移瘤和异种移植物来源于原发性肿瘤。转移包含两个新的突变和一个大的缺失不存在于原发性肿瘤，并显着富集20个共享的突变。异种移植物保留了所有原发肿瘤突变，并显示出类似于转移的突变富集模式。两个重叠的大缺失，包括CTNNA1，存在于所有三个肿瘤样本。与原发性肿瘤相比，转移和异种移植中的差异突变频率和结构变异模式表明继发性肿瘤可能来自原发性肿瘤内的少数细胞。