Cellular hierachy of ER- breast cancers in different ethnic groups

描述（由申请人提供）：正常干细胞和至少一些癌细胞必须能够自我更新。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，正常干细胞中组织中干细胞的总数受到高度调节，并且超出正常水平的扩增受到遗传程序的限制[6]，癌症中自我更新细胞的持续扩增导致肿瘤的发展。自我更新癌细胞有两种可能的起源细胞。首先，癌症可能是由正常的干细胞引起的，这些干细胞已经失去了自我更新的遗传限制。其次，癌症可能是由获得自我更新能力的祖细胞引起的。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乳腺上皮和新生乳腺肿瘤的细胞层次。在这项研究中，我们将使用这项技术来比较不同种族的ER-，PR-，ERB-B2-（三阴性）乳腺肿瘤与正常乳腺上皮中发现的细胞类型的细胞层次。这些知识可能会导致对乳腺癌治疗的新见解。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确定正常人上皮细胞的层次结构。 具体目标#2：利用单细胞基因组学技术了解不同种族人群ER-PR-ERB-B2-（三阴性，基底细胞）乳腺癌的细胞层次。

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.