Cellular hierachy of ER- breast cancers in different ethnic groups

不同种族ER-乳腺癌的细胞层次

• 批准号: 8719946
• 负责人: MICHAEL CLARKE
• 金额: $ 45.53万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-29 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719946
• 关键词: Address; African American; Basal Cell; Breast; Breast Cancer Cell; Breast Cancer Treatment; Caucasians; Caucasoid Race; Cells; Complex; Data; Development; Duct (organ) structure; Epithelium; Ethnic Origin; Ethnic group; Gene Expression; Genetic; Genetic Programming; Genomics; Goals; Grant; Hispanics; Human; Human Mammary Epithelium; Knowledge; Laboratories; Lead; Malignant Neoplasms; Mammary Neoplasms; Multipotent Stem Cells; Myoepithelial cell; Population; Race; Stem cells; Technology; Tissues; Universities; cancer cell; cell type; cytokine; insight; malignant breast neoplasm; progenitor; receptor; self renewing cell; self-renewal; triple-negative invasive breast carcinoma; tumor

DESCRIPTION (provided by applicant): Both normal stem cells and at least some of the cancer cells must be able to self renew. The difference between a self renewing normal stem cell and a self renewing cancer cell is that unlike normal stem cells in which the total number of stem cells in a tissue is highly regulated and expansion beyond the normal level is restricted by genetic programs [6], there is a continuous expansion of self renewing cells in cancer resulting in the development of a tumor. There are 2 possible cells of origin for the self renewing cancer cells. First, it is possible that the cancers arise from normal stem cells that have lost the genetic constraints on self renewal. Next, it is possible that cancers arise from progenitor cells that have acquired the ability to self renew. Our laboratories have used single cell genomics to begin to define the cellular hierarchy of the normal human breast epithelium and de novo breast tumors. In this grant, we will use this technology in order to compare the cellular hierarchies of ER-,PR-, ERB-B2- (triple negative) breast tumors of different ethnicities to the cell types found in nonnal breast epithelium. This knowledge may lead to new insights into the treatment of breast cancer. The following specific aims will address those goals. Specific Aim # 1: To use single cell genomics technology to define the cellular hierarchy of normal human epithelium. Specific Aim #2: To use single cell genomics technology to understand the cellular hierarchy of ER-PR-ERB-B2- (triple negative, basal cell) breast cancer in different racial groups.

描述（由申请人提供）：正常干细胞和至少一些癌细胞都必须能够自我更新。自我更新的正常干细胞和自我更新的癌细胞之间的区别在于，与正常干细胞不同，组织中干细胞的总数受到高度调控，超出正常水平的扩张受到遗传程序的限制[6]，癌症中自我更新细胞不断增殖，导致肿瘤的发展。自我更新的癌细胞有两种可能的起源细胞。首先，癌症可能是由失去自我更新遗传限制的正常干细胞引起的。其次，癌症有可能是由具有自我更新能力的祖细胞产生的。我们的实验室已经使用单细胞基因组学来开始定义正常人类乳腺上皮和新生乳腺肿瘤的细胞层次结构。在这笔资助中，我们将使用这项技术来比较不同种族的 ER-、PR-、ERB-B2-（三阴性）乳腺肿瘤的细胞层次结构与非正常乳腺上皮细胞类型。这些知识可能会给乳腺癌治疗带来新的见解。以下具体目标将实现这些目标。 具体目标#1：使用单细胞基因组学技术来定义正常人类上皮的细胞层次结构。 具体目标#2：利用单细胞基因组学技术了解不同种族群体中 ER-PR-ERB-B2-（三阴性、基底细胞）乳腺癌的细胞层次结构。

项目成果

Simultaneous single-molecule epigenetic imaging of DNA methylation and hydroxymethylation.

DNA 甲基化和羟甲基化的同步单分子表观遗传学成像。

• 发表时间: 2016-04-19
• 影响因子: 11.1
• 作者: Song, Chun;Diao, Jiajie;Brunger, Axel T;Quake, Stephen R
• 通讯作者: Quake, Stephen R

5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages.

无细胞 DNA 中的 5-羟甲基胞嘧啶特征提供有关肿瘤类型和阶段的信息。

• 发表时间: 2017-10
• 影响因子: 44.1
• 作者: Song, Chun;Yin, Senlin;Ma, Li;Wheeler, Amanda;Chen, Yu;Zhang, Yan;Liu, Bin;Xiong, Junjie;Zhang, Weihan;Hu, Jiankun;Zhou, Zongguang;Dong, Biao;Tian, Zhiqi;Jeffrey, Stefanie S;Chua, Mei;So, Samuel;Li, Weimin;Wei, Yuquan;Diao, Jiaj
• 通讯作者: Diao, Jiaj