VIROLOGY AND GENETICS OF CANCER

越来越多的分子导向的病毒学和遗传学研究， 过去15年的计划使我们达到了这样一个地步， 这次更新计划的主要内容是利用分子技术 在病毒学和遗传学中定义了一系列关键基因， 癌细胞的遗传损伤导致生长失调 控制我们在更新计划中的总体目标是了解 这些关键基因的正常功能，以及它们的改变如何导致 肿瘤或其他异常，因此药理学或遗传学方法 干预可以设计和测试，为治疗提供依据， 干预项目1将定义和表征基因激活 导致骨髓性白血病的前病毒插入;第一个基因 其特征在于该项目是homebox基因亚家族的一个新成员。 该亚家族由PBX 1定义，PBX 1是参与染色体的基因， 易位导致人前B细胞白血病。项目2将 表征在胚胎造血干细胞中表达的基因， 研究其在造血分化中作用以及作为 干细胞标志物项目3将识别和表征黑色素瘤 染色体9 p21区域中的抑制基因，并在正常人中研究功能 和恶性细胞;双重方法将涉及表征 p16基因在家族性黑色素瘤中的作用 另一个9 p21抑制基因的鉴定，可能具有直接的 在几种形式的瘤形成中的作用。项目4，这是一个新的项目， 修订，旨在克隆和表征参与致死性 斑点（是突变，一种鼠，一种与人类相似的鼠疾病 先天性巨结肠;已知先天性巨结肠的一种形式 涉及RET癌基因，该基因与几种家族性肿瘤有关。 每一个项目都涉及基因的克隆和鉴定， 在生长、分化或瘤形成中起关键作用。表达及 对这些克隆位点中的每一个进行功能研究以及基因定位 将通过项目之间的互动进行， 促进的成本、技术、专门知识和想法共享的优势， 计划项目结构。

Increasingly molecularly oriented virology and genetic studies in this program of the last fifteen years have brought us to the point that our main theme in this revised renewal program is to use molecular techniques in virology and genetics to define a series of critical genes, at which genetic lesions in cancer cells have led to dysregulation of growth control. Our overall goal in the renewal program is to understand the normal function of these critical genes, and how their alterations leads to neoplasia or other abnormality, so that pharmacological or genetic methods to intervene can be devised and tested, to provide a basis for therapeutic intervention. Project 1 will define and characterize genes activated by proviral insertion that result in myeloid leukemia; the first gene characterized by the project is a novel member of a homebox gene subfamily. This subfamily is defined by PBX1, a gene involved in chromosome translocation resulting in human Pre B cell leukemia. Project 2 will characterize a gene expressed in embryonic hematopoietic stem cells, investigate its role in hematopoietic differentiation and function as a stem cell marker. Project 3 will identify and characterize melanoma tumor suppressor gene(s) in chromosome region 9p21 and study function in normal and malignant cells; the dual approach will involve characterization of the role of the p16 gene in familial melanoma in three kindreds and identification of another 9p21 suppressor gene, likely to have a direct role in several forms of neoplasia. project 4, a new project in this revision, aims to clone and characterize the gene involved in the lethal spotting (Is mutation, a murine, a murine disease similar to human Hirschsprung's disease; one form of Hirschsprung's disease is known to involve the RET oncogene which is involved in several familial neoplasias. Each of the projects involves cloning and characterization of genes with critical roles in growth, differentiation or neoplasia. Expression and functional studies, as well as gene mapping, for each of these cloned loci will be performed through interactions among the projects, taking maximum advantage of the cost, technology, expertise and idea-sharing promoted by the Program Project structure.