VIROLOGY AND GENETICS OF CANCER

这方面的病毒学和遗传学研究越来越以分子为导向 过去十五年的计划使我们达到了这样的程度： 修订后的更新计划的主题是使用分子技术 在病毒学和遗传学中定义了一系列关键基因，其中 癌细胞的基因损伤导致生长失调 控制。我们更新计划的总体目标是了解 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，因此药物或遗传学方法 可以设计和测试干预措施，为治疗提供基础 干预。项目 1 将定义和表征由以下物质激活的基因 前病毒插入导致骨髓性白血病；第一个基因 该项目的特点是 homebox 基因亚家族的新成员。 该亚家族由 PBX1 定义，PBX1 是一个涉及染色体的基因。 易位导致人类前 B 细胞白血病。项目2将 表征胚胎造血干细胞中表达的基因， 研究其在造血分化中的作用和作为造血细胞的功能 干细胞标记。项目 3 将识别和表征黑色素瘤 染色体区域 9p21 中的抑制基因和正常情况下的研究功能 和恶性细胞；双重方法将涉及表征 p16基因在三个家族的家族性黑色素瘤中的作用 鉴定出另一个 9p21 抑制基因，可能具有直接作用 在多种形式的肿瘤中发挥作用。项目4，这是一个新项目 修订，旨在克隆和表征涉及致死性的基因 斑点（是突变，鼠类，与人类相似的鼠类疾病 先天性巨结肠症；已知先天性巨结肠症的一种形式是 涉及 RET 癌基因，该基因与多种家族性肿瘤有关。 每个项目都涉及基因的克隆和表征 在生长、分化或肿瘤形成中发挥关键作用。表达和 对每个克隆位点进行功能研究以及基因图谱 将通过项目之间的互动来执行，最大限度地利用 成本、技术、专业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.