Multigenic copy number alterations

多基因拷贝数改变

基本信息

  • 批准号:
    9333598
  • 负责人:
  • 金额:
    $ 55.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-03-15 至 2022-02-28
  • 项目状态:
    已结题

项目摘要

Project Summary DNA copy number alterations (CNAs) are oncogenic drivers for many types of human cancer. For some cancers, e.g. certain ovarian, breast and endometrial cancers, it is very likely that CNAs, comprise the bulk of genetic alterations responsible for their highly malignant properties. CNAs may also be responsible for driving squamous carcinoma of the lung and for subsets of gastric and esophageal cancers. Relatively little attention is being paid to understanding this class of genetic alterations. More importantly, from a cancer treatment perspective, there is no roadmap for determining whether they induce selective dependencies that could be utilized for developing new therapeutics. As our group and others have discovered in the past several years, the vast majority of CNAs contain multiple driver genes, and this makes it considerably more difficult to study how they impact cancer progression compared to single-gene events. The overall goal of this project is to develop new tools and models to investigate multigenic CNAs so that they can be more readily studied and utilized in developing new therapeutics. In Aim 1, we will combine CRISPR/Cas9 and Cre-Lox genome engineering to accurately model multigenic CNAs and determine how they impact oncogenic phenotypes in normal mammary epithelial cells, similar to how mutations in single-gene alterations such as PIK3CA are currently studied. Once we have validated these new cell models, we will screen for induced dependencies. In Aim 2, we will develop and implement computational methods to extract information about specific CNAs from the warehouse of information present in large-scale integrated cancer genome datasets. We have extensive preliminary results that validate this approach, including the prediction of CNA-selective dependencies. Lastly, to truly understand how multigenic CNAs play a role in cancer, we must functionally probe the interactions between multiple drivers. We previously demonstrated that these interactions were key features of the oncogenicity of the 14q13 amplicon in lung cancer and 11q13 amplicon in liver cancer. Thus, our final goal is to develop and implement generalizable methods to study genetic interactions between multiple drivers (Aim 3). Our proposal is based on the premise that CNAs are important drivers in cancer but that the current research approach needs to be improved. The clinical effectiveness of targeted treatments for patients with HER2-amplified breast cancers underscores the enormous translational potential of CNAs. By developing the tools and models for CNAs described in this proposal, we will make a significant impact on understanding multigenic CNAs and will lay the groundwork for identifying associated dependencies and therapeutic strategies.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Scott Powers其他文献

Scott Powers的其他文献

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{{ truncateString('Scott Powers', 18)}}的其他基金

Multigenic copy number alterations
多基因拷贝数改变
  • 批准号:
    10115639
  • 财政年份:
    2017
  • 资助金额:
    $ 55.2万
  • 项目类别:
Core D
  • 批准号:
    8744325
  • 财政年份:
    2013
  • 资助金额:
    $ 55.2万
  • 项目类别:
COMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETS
验证癌症基因组目标的计算和功能方法
  • 批准号:
    8593329
  • 财政年份:
    2012
  • 资助金额:
    $ 55.2万
  • 项目类别:
COMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETS
验证癌症基因组目标的计算和功能方法
  • 批准号:
    8464686
  • 财政年份:
    2012
  • 资助金额:
    $ 55.2万
  • 项目类别:
COMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETS
验证癌症基因组目标的计算和功能方法
  • 批准号:
    8660049
  • 财政年份:
    2012
  • 资助金额:
    $ 55.2万
  • 项目类别:
COMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETS
验证癌症基因组目标的计算和功能方法
  • 批准号:
    8874159
  • 财政年份:
    2012
  • 资助金额:
    $ 55.2万
  • 项目类别:
Genomics and Proteomics
基因组学和蛋白质组学
  • 批准号:
    8234425
  • 财政年份:
    2012
  • 资助金额:
    $ 55.2万
  • 项目类别:
COMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETS
验证癌症基因组目标的计算和功能方法
  • 批准号:
    8323765
  • 财政年份:
    2012
  • 资助金额:
    $ 55.2万
  • 项目类别:
CSHL Molecular Target Discovery and Development Center
CSHL分子靶点发现与开发中心
  • 批准号:
    7863581
  • 财政年份:
    2009
  • 资助金额:
    $ 55.2万
  • 项目类别:
CSHL Molecular Target Discovery and Development Center
CSHL分子靶点发现与开发中心
  • 批准号:
    7944129
  • 财政年份:
    2009
  • 资助金额:
    $ 55.2万
  • 项目类别:

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多基因拷贝数改变
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  • 财政年份:
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鏡像四肢多指趾症の遺伝子単離
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    1999
  • 资助金额:
    $ 55.2万
  • 项目类别:
    Grant-in-Aid for Exploratory Research
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