了解端粒功能障碍的替代非同源末端连接修复-猫眼课题宝

了解端粒功能障碍的替代非同源末端连接修复

批准号：

8756430

负责人：

Sandy S Chang

金额：

$21.73万

依托单位：

YALE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2014

资助国家：

美国

项目状态：

已结题

起止时间：

2014-07-01 至 2016-06-30

来源：

https://reporter.nih.gov/project-details/8756430

关键词：

7-Hydroxystaurosporine Address Affect American BRCA1 gene Biological Assay Breast Breast Cancer Cell Cancer Patient Cancer cell line Candidate Disease Gene Cell Line Characteristics Chromosome abnormality Complex DNA Damage DNA Double Strand Break DNA Repair DNA Repair Pathway DNA Sequence Rearrangement Data Defect Disease Epithelium Estrogens Event Excision Frequencies Functional disorder Generations Genes Genome Genome Stability Genomic Instability Genomics Health Homeostasis Human In Vitro Knowledge Length Maintenance Malignant Neoplasms Mammary Neoplasms Mediating Molecular Analysis Monitor Mouse Mammary Tumor Virus Mus Mutation Nonhomologous DNA End Joining Oncogenic Pathway interactions Pharmaceutical Preparations Play Progesterone Proteins Recurrence Repression Role Sampling Signal Transduction Site Somatic Mutation Structural Chromosomal Abnormality Telomere Maintenance Telomere Shortening Telomere-Binding Proteins Testing Woman base cancer initiation homologous recombination in vivo inhibitor/antagonist loss of function malignant breast neoplasm mammary epithelium mouse model mutant novel therapeutics outcome forecast programs public health relevance reconstitution repaired response telomere triple-negative invasive breast carcinoma tumor tumor growth tumor initiation tumor progression tumorigenesis

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中文摘要

翻译

描述（由申请人提供）：三阴性乳腺癌（TNBC）仅包括所有乳腺癌的一个子集，但它们具有高度侵袭性，预后最差。TNBC的一个典型特征是其惊人复杂的基因组谱，突出表现为基因组重排和染色体结构畸变。然而，可能驱动肿瘤发生的染色体改变的机制仍不清楚。我们假设TNBC依赖于替代的、Lig 4-独立的NHEJ（A-NHEJ）途径进行DNA修复。我们将使用小鼠模型和人类肿瘤样本来了解进行性端粒功能障碍和A-NHEJ通路的激活如何产生促癌染色体畸变以及突变变化的逐步积累，从而有利于乳腺肿瘤的发生和进展。

英文摘要

DESCRIPTION (provided by applicant): Triple negative breast cancers (TNBCs) comprise only a subset of all breast cancers, yet they are highly aggressive and offer the worst prognosis. A characteristic feature of TNBCs is their strikingly complex genomic profiles, highlighted by genomic rearrangements and chromosome structural aberrations. However, mechanisms responsible for the chromosomal alterations that potentially drive tumorigenesis remain unclear. We postulate that TNBCs depend upon the alternative, Lig4-independent NHEJ (A-NHEJ) pathway for DNA repair. We will use mouse models and human tumor samples to understand how progressive telomere dysfunction and activation of the A-NHEJ pathway generate pro-oncogenic chromosomal aberrations and the stepwise accumulation of mutational changes in favor of breast tumor initiation and progression.

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