Tumor Suppressors in Lymphocytes

淋巴细胞中的肿瘤抑制因子

基本信息

批准号：
7325816
负责人：
MATTHIAS R WABL
金额：
$ 26.59万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-05 至 2009-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7325816
关键词：
Affect Alleles Anchored Polymerase Chain Reaction Animals B-Cell Lymphomas Breeding Cells Chemicals Chromosome Mapping DNA Depth Diploidy Dose Ethylnitrosourea Event Exposure to Female Genes Genetic Predisposition to Disease Genome Genomics Goals Growth Haploidy Haplotypes Hereditary Malignant Neoplasm Human Infection Insertional Mutagenesis Lead Lymphocyte Lymphoma Malignant Neoplasms Murine leukemia virus Mus Mutagenesis Mutate Mutation Mutation Analysis Nature Neonatal Oncogenes Organism Partner in relationship Pathway interactions Personal Satisfaction Polymerase Chain Reaction Predisposition Proto-Oncogenes Research Personnel Retroviridae Signal Pathway Signal Transduction Site Suppressor Genes Suppressor-Effector T-Lymphocytes Techniques Time Tumor Suppressor Genes Tumor Suppressor Proteins Tumor-Suppressor Gene Inactivation Viral Viral Genome base cell growth genome sequencing lymphoid neoplasm male sperm cell tumor tumorigenesis

项目摘要

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.

淋巴细胞中的肿瘤抑制因子正常、受控细胞生长所必需的基因称为肿瘤抑制基因，这些基因的失活会导致肿瘤的形成。大多数已知的肿瘤抑制因子是通过对具有遗传性癌症倾向的生物体进行基因图谱定位。然而，家族癌症易感性仅导致约 10% 的人类癌症，并且识别涉及非家族性癌症的肿瘤抑制因子的作用速度较慢。该提案的目标是定义一组肿瘤抑制因子被删除后会导致小鼠淋巴细胞肿瘤的形成；和它们与原癌基因的相互作用尽可能完全。这将通过逆转录病毒插入诱变与化学诱变相结合来尝试，以使给定小鼠细胞中的两个等位基因失活。经过化学诱变的雄性小鼠的后代是通过逆转录病毒进行插入突变，诱导淋巴细胞来源的肿瘤。病毒式传播基因组破坏潜在的抑制基因，导致其失活，同时产生用于识别插入位点的标记。标记的癌症基因将通过高通量克隆和测序基于通量PCR的技术。随后，其中的一个子集将被进一步表征，其性质它们与其他癌基因的合作（共突变）将被确定。