Cancer Genetics Program

癌症遗传学计划

• 批准号: 9975722
• 负责人: Adam Charles Siepel
• 金额: $ 4.05万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9975722
• 关键词: Animal Model; Award; Behavioral; Bioinformatics; Breast; Cancer Center; Cancer Center Support Grant; Cancer Diagnostics; Cancer Model; Cell Line; Cells; Chromatin; Chromosomes; Clinical; Colon; Complement; Complex; Data; Development; Diagnosis; Disease; Disease Progression; Engineering; Epigenetic Process; Family; Gene Expression; Genetic; Genetic Polymorphism; Genetic study; Genome; Goals; Heterogeneity; Journals; Laboratories; Lead; Malignant Neoplasms; Maps; Measures; Methylation; Modeling; Modification; Monitor; Mosaicism; Mouse Models of Human Cancer Consortium; Mus; Mutation; Nature; Nucleotides; Organ; Pancreas; Pathway interactions; Patients; Pattern; Peer Review; Positioning Attribute; Premalignant Cell; Prognostic Marker; Prostate; Publications; Publishing; RNA Interference; RNA Splicing; Recurrence; Research; Research Personnel; Resistance; Risk; Science; Societies; Source; Structure; System; Techniques; Technology; The Cancer Genome Atlas; Therapeutic; Tumor Suppression; Tumor Suppressor Genes; United States National Institutes of Health; Variant; cancer cell; cancer genetics; cancer genome; cancer genomics; cancer prevention; diagnostic biomarker; epigenome; genomic data; high dimensionality; improved; in vivo; individualized medicine; innovation; insertion/deletion mutation; leukemia/lymphoma; liquid biopsy; machine learning method; member; mouse model; neoplastic cell; new therapeutic target; next generation; novel diagnostics; novel strategies; predictive marker; programs; single cell analysis; single cell sequencing; single molecule; small hairpin RNA; technology development; therapeutic target; transcriptome; tumor; tumor heterogeneity; tumor progression; tumorigenesis

Cancer Genetics Program - Project Summary/Abstract Cancer is, at its most fundamental level, a disease of the genome. The central goal of the Cold Spring Harbor Laboratory (CSHL) Cancer Genetics Program (CG) is to use information contained within the cancer genome to improve our understanding and treatment of the disease. Our multifaceted approach includes mapping the specific pathways involved in different forms of cancer, developing new diagnostic markers and therapeutic strategies for cancer cells, and technology development for monitoring the progression of the disease. Many members maintain strong research programs in the discovery of cancer-specific variations, ranging from single nucleotide and small indel polymorphisms to copy number changes to modification of the epigenome. A particular strength of the CG Program is in the analysis of the heterogeneity of tumors revealed through single cell analysis. This heterogeneity is proving to be especially important in the clinical setting as it often contributes to disease progression and therapy resistance. Complementary to the experimental strengths of the Program, the Program is also expert at developing computational approaches to identify and model the most important alterations. Drivers of tumor development are functionally validated, most often in the mouse, using strategies, many developed within the CG Program, which encompass chromosome engineering (e.g., for copy number or structural variations), mosaic mouse models with expressed oncogenes and tumor suppressors regulated in vivo with shRNAs. Completely unbiased functional approaches are also taken by several groups to discover novel therapeutic targets using well characterized cultured cell lines, mosaic animal models, and primary patient tumor grafts. Finally, several CG Program investigators approach the problem of cancer prevention by looking at genetic and behavioral modifiers of risk. The premier position of CG Program investigators in employing many of these strategies is recognized by their lead involvement in national projects including the Mouse Models of Human Cancer Consortium (MMHCC), the cancer genome atlas (TCGA), Stand Up to Cancer, the Leukemia and Lymphoma Society program projects, the STARR consortium, as well as many similar awards from the NCI, the NIH, the DOD, and the NSF. The CG Program has sixteen members. As of 8/1/15, CG members received $2.3M in direct support from NCI and other peer-reviewed sources, and $0.8M in additional cancer-related support. Since 9/1/10, the CG Program published 148 cancer-related articles, 49 (33%) involved multiple CCSG members; 29 (20%) intra- programmatic, and 25 (17%) inter-programmatic. Forty CG publications appeared in the highest profile journals (Science, Cell and Nature families). During the next five years, the CG Program will continue its tradition of innovation and impact, but in a manner that will require continued support of the CSHL Cancer Center.

癌症遗传学计划-项目摘要/摘要 癌症在最基本的层面上是一种基因组疾病。冷泉港的中心目标 癌症遗传学计划（CG）是利用癌症基因组中包含的信息 来提高我们对疾病的认识和治疗。我们的多方面方法包括绘制 参与不同形式癌症的特定途径，开发新的诊断标志物和治疗方法， 针对癌细胞的策略，以及监测疾病进展的技术开发。 许多成员在发现癌症特异性变异方面保持着强有力的研究计划，范围从 单核苷酸和小插入缺失多态性到拷贝数改变到表观基因组的修饰。一 CG程序的特别优势在于通过单个肿瘤的异质性分析， 细胞分析这种异质性在临床环境中被证明是特别重要的，因为它通常 有助于疾病进展和治疗抗性。补充的实验优势， 该计划还擅长开发计算方法，以确定和模拟 最重要的改变肿瘤发展的驱动因素在功能上得到了验证，最常见的是在小鼠中， 使用策略，许多在CG计划中开发的策略，包括染色体工程（例如， 对于拷贝数或结构变异），具有表达的癌基因和肿瘤的嵌合小鼠模型 在体内用shRNA调控的抑制子。完全无偏的函数方法也被 几个小组发现新的治疗目标，使用良好表征的培养细胞系，嵌合动物 模型和原发性患者肿瘤移植物。最后，几个CG程序研究人员的方法的问题， 通过研究遗传和行为因素来预防癌症。 CG项目研究人员在采用其中许多策略方面的首要地位得到了他们的认可 领导参与国家项目，包括人类癌症小鼠模型联盟（MMHCC）， 癌症基因组图谱（TCGA），站起来对抗癌症，白血病和淋巴瘤协会计划项目， STARR财团，以及来自NCI、NIH、DOD和NSF的许多类似奖项。 CG计划有16名成员。截至2015年8月1日，CG成员从NCI获得了230万美元的直接支持 和其他同行评审来源，以及80万美元的额外癌症相关支持。自2010年9月1日以来，CG 该项目发表了148篇癌症相关文章，49篇（33%）涉及多个CCSG成员; 29篇（20%）内部 25个（17%）方案间。40篇CG出版物出现在最高知名度的期刊上 （科学，细胞和自然家庭）。在接下来的五年里，CG计划将继续其传统， 创新和影响，但在某种程度上，将需要CSHL癌症中心的持续支持。