VIROLOGY AND GENETICS OF CANCER

日益以分子为导向的病毒学和遗传学研究 过去十五年的计划把我们带到了这样一个地步：我们的 修订后的更新计划的主要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，在这些基因 癌细胞中的基因损伤导致生长失调 控制力。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，以及它们的变化如何导致 肿瘤或其他异常，使药理或遗传方法 干预可以设计和测试，为治疗提供依据 干预。项目1将定义和描述由以下因素激活的基因 导致髓系白血病的前病毒插入；第一个基因 该项目的特征是Homebox基因亚家族的一个新成员。 这个亚家族是由Pbx1基因定义的，Pbx1基因与染色体有关 易位导致人类前B细胞白血病。项目2将 描述了在胚胎造血干细胞中表达的基因， 研究其在造血细胞分化中的作用及其作为一种 干细胞标记物。项目3将识别和描述黑色素瘤的特征 染色体9p21区的抑制基因S及其在正常人群中的功能研究 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9p21抑制基因的鉴定，可能有一个直接的 在几种形式的肿瘤中起作用。项目4，这个项目中的一个新项目 修订的目的是克隆和鉴定与致命病毒有关的基因 斑点(是一种突变，一种类似于人类的一种鼠类疾病 先天性巨结肠症；一种形式的先天性巨结肠症 涉及RET癌基因，该基因与几种家族性肿瘤有关。 每个项目都涉及到基因的克隆和表征 在生长、分化或肿瘤形成中的关键作用。表达式和 对每个克隆的基因座进行功能研究和基因定位 将通过项目之间的互动来执行，最大限度地 推动的成本、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.