CANCER GENETICS PROGRAM

越来越清楚的是，癌症是一种复杂的遗传疾病，不仅因为不同的组织学类型的数量，而且还因为个体之间的遗传和表型变异，这些变异可以影响疾病发展的易感性，肿瘤进展或对治疗的反应。在肿瘤中的体细胞遗传事件和基因表达变化的组合水平以及在正常宿主DNA中的遗传性遗传变异（SNP）的模式中都可以看到异质性。此外，宿主的遗传学和环境暴露之间存在复杂的相互作用，导致肿瘤易感性。癌症遗传学计划致力于阐明肿瘤易感性、肿瘤发生和进展的遗传学，并利用这些信息在临床上改善癌症管理。该计划汇集了36名计划成员，他们在先进的基因组和遗传分析工具的应用方面具有专业知识，以利用UCSF优秀的临床和患者资源来识别有助于癌症发生和进展的异常。该计划还与UCSF的癌症组小鼠模型有密切联系，我们正在共同建立一种比较小鼠-人类易感性遗传学的方法。 已经发起了一项新的重大努力， 系统遗传学方法对癌症，与劳伦斯伯克利国家 实验室（LBNL）。项目负责人确定了以下四个中心主题，我们的目标是 在未来五年内发展：（1）癌症易感性的生殖系和环境决定因素（约翰 Witte）;（2）癌症基因组和表观基因组分析（Donna Albertson和Joseph Costello）;（3）系统 癌症遗传学（Joe Gray和Allan巴尔曼）;（4）大规模癌症分析的统计方法 癌症数据集（Neil Risch和Ajay Jain）。该计划的成员是完全融入器官网站特定 计划，并广泛参与联合研讨会和讨论小组与人类遗传学 程序.此外，该方案每月组织一次癌症遗传学讨论论坛，以期 鼓励交叉研究，包括生殖系和体细胞方法， 了解癌症的遗传学该计划有$12，940，579总同行评审的支持，最后 预算年度。该方案有17%的方案内和43%的方案间出版物。

It is becoming increasingly clear that cancer is a complex genetic disease, not just because of the number of distinct histological types, but also because of genetic and phenotypic variation between individuals that can influence susceptibility to disease development, tumor progression or responses to therapy. Heterogeneity is seen both at the level of the combinations of somatic genetic events and gene expression changes in tumors, and in the patterns of inherited genetic variants (SNPs) in the normal host DNA. In addition, complex interactions exist between the genetics of the host and environmental exposures that contribute to tumor susceptibility. The Cancer Genetics Program is dedicated to the elucidation of the genetics of tumor susceptibility, tumorigenesis and progression, and to the utilization of this information clinically to improve cancer management. The program brings together 36 program members with expertise in the application of advanced genomic and genetic analysis tools to identify abnormalities that contribute to cancer genesis and progression, utilizing the outstanding clinical and patient resources at UCSF. The program also has close contact with the mouse models of cancer group at UCSF, and together we are building a comparative mouse-human approach to the genetics of susceptibility. A major new effort has been launched to develop a Systems Genetics approach to cancer, in close collaboration with the Lawrence Berkeley National Laboratory (LBNL). The Program Leaders have identified the following four central themes that we aim to develop in the next five years: (1) germline and environmental determinants of cancer susceptibility (John Witte); (2) cancer genome and epigenome analysis (Donna Albertson and Joseph Costello); (3) systems genetics of cancer (Joe Gray and Allan Balmain); and (4) statistical approaches to analysis of large scale cancer data sets (Neil Risch and Ajay Jain). The Program Members are fully integrated into the organ-sitespecific programs, and participate broadly in joint seminars and discussion groups with the human genetics program. In addition, the Program organizes a monthly cancer genetics discussion forum, with a view to encouraging cross-cutting research that encompasses both germline and somatic approaches to understanding the genetics of cancer. The Program has $12,940,579 Total peer reviewed support for the last budget year. The Program has 17% intra-programmatic and 43% inter-programmatic publications.