Tumor Suppressors in Lymphocytes

淋巴细胞中的肿瘤抑制因子 正常的、受控的细胞生长所必需的基因被称为肿瘤抑制基因， 这些基因的失活可导致肿瘤形成。大多数已知的肿瘤抑制剂是 通过对具有癌症遗传易感性的生物体进行遗传图谱定位。然而，家族 癌症易感性仅占人类癌症的约10%， 涉及非家族性癌症的肿瘤抑制剂的进展较慢。该提案的目的是定义 一组肿瘤抑制因子，当其缺失时会导致小鼠淋巴细胞肿瘤的形成; 它们与原癌基因的相互作用。 这将尝试通过逆转录病毒插入诱变，结合化学诱变， 在给定小鼠的细胞中检测两个等位基因。化学诱变雄性小鼠的后代 通过逆转录病毒进行插入突变，诱导淋巴细胞来源的肿瘤。病毒 基因组破坏潜在的抑制基因，导致它们失活，同时产生一个 用于鉴定插入基因座的标记。标记的癌症基因将被克隆和测序， 基于通量PCR的技术。随后，将进一步描述其中的一个子集， 将确定它们与其他致癌基因（共突变）的合作。

Tumor suppressors in lymphocytes The genes that are necessary for normal, controlled cell growth are called tumor suppressor genes, and inactivation of these genes can lead to tumor formation. The majority of known tumor suppressors were located by the genetic mapping of organisms with an inherited predisposition for cancer. However, familial predisposition to cancer is responsible for only approximately 10% of human cancers and identificationof tumor suppressors involved in non-familial cancers has been slower. The goal of this proposal is to define the set of tumor suppressors that when deleted contributeto the formation of lymphocytetumors in mice; and their interactions with protooncogenes, as completely as possible. This will be attempted by retroviral insertionalmutagenesis, combined with chemical mutagenesis, to inactivate both alleles in cells of a given mouse. The offspring of chemically mutagenized male mice are subjected to insertional mutagenesis by retrovirus that induces tumors of lymphocyte origin. The viral genome disrupts potential suppressor genes, leading to their inactivation, and at the same time creates a marker for identifying the insertion loci. The tagged cancer genes will be cloned and sequenced by a high throughput PCR based technique. Subsequently, a subset of them will be further characterized and the nature of their cooperation with other oncogenes (co-mutations) will be determined.