Identification of Significant Race Associated Colon Cancer Drive Gene Mutations

显着种族相关结肠癌驱动基因突变的鉴定

• 批准号: 8330850
• 负责人: JOSEPH EDWARD WILLIS
• 金额: $ 10.24万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-09 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330850
• 关键词: Address; African; African American; Applications Grants; Area; Basic Science; Behavior; Bioinformatics; Biological; Biological Markers; Cancer Biology; Cancer Patient; Caucasians; Caucasoid Race; Classification; Clinical; Colon Carcinoma; Communities; Comprehensive Cancer Center; DNA; Dependency; Development; Disease; Environmental Exposure; Environmental Risk Factor; Epidemiology; Etiology; European; Exploratory/Developmental Grant; Faculty; Formalin; Future; Gene Mutation; Genes; Genetic; Genetic Processes; Goals; Growth; Hereditary Disease; Human; Hybrids; Incidence; Individual; Institution; Investigation; Life Style; Link; Malignant Neoplasms; Mediating; Medical center; Medicine; Molecular; Monitor; Morbidity - disease rate; Mutate; Mutation; NIH Program Announcements; Oncogenes; Outcome; Paraffin Embedding; Pathogenesis; Pathway interactions; Patients; Pattern; Population; Positioning Attribute; Predisposition; Race; Recurrence; Research; Research Infrastructure; Specimen; System; Technology; Testing; Tissues; Tumor Suppressor Genes; Work; base; biobank; cancer cell; cancer health disparity; carcinogenesis; caucasian American; colon carcinogenesis; design; innovation; knowledge base; member; mortality; mutant; next generation; oncology; programs; racial and ethnic; tumor; tumor progression

DESCRIPTION (provided by applicant): This application addresses the Program Announcement - Exploratory/Developmental Grants Program for Basic Research in Cancer Health Disparities. PA Number: PAR-09-160. The grant proposal is entitled: 'Identification of Significant Race Associated Colon Cancer Driver Gene Mutations'. The goal of this proposal is to test the hypothesis that patterns of driver gene [CAN gene] mutations differ among colon cancers arising in individuals of different race, reflecting at the molecular level differences in disease epidemiology, lifestyle, and environmental exposures among these groups. CRC is one of the common cancers with significant disparities attributed to racial/ethnic etiologic factors. African Americans have a significantly higher incidence of morbidity and mortality caused by CRC than the Caucasian population. Tumor CAN gene mutation profiles are directly related to cancer progression and clinical behavior in virtually all cancer systems. Our recent identification of the 140 CRC CAN genes and our ability to molecularly stratify CRC patients in terms of racial heritage - as well as using patient self-declared status - places us in a unique position to look at the influence of race on this fundamental aspect of cancer biology. Furthermore we have developed the ability to assess the influence of a patient's ancestry on individual tumor CAN gene mutations. The aim of this proposal will be to sequence the 140 CAN genes in a matched set of CRCs from African Americans and Caucasians. These patients will be initially stratified by self-declared race. Furthermore, these patients will be reclassified based on each individual's African and European Ancestry Informative Markers. These studies are enabled by a number of different efforts by our group. We have constructed a large, well-annotated, biorepository containing colon cancer tissue specimens from patients treated at a large medical center over the last 20 years. The majority of these specimens are formalin-fixed paraffin embedded tissues [FFPE]. Over the last few years we worked to develop sophisticated approaches to enhance the reliability of DNA extraction from FFPE materials. In tandem with these efforts we developed an infrastructure and knowledge base to support high throughput sequencing such as envisioned in this proposal. This includes the acquisition of a 'Next Generation' sequencer and hiring of faculty members to further extend the depth of expertise in this area at our institution. This proposal has the potential to significantly advance the understanding of the effects of racial/ethnic predisposition in cancers overall and in CRC - the second most common human cancer.

说明（由申请人提供）：本申请涉及计划公告 - 癌症健康差异基础研究探索性/发展资助计划。 PA 编号：PAR-09-160。该拨款提案的标题是：“显着种族相关结肠癌驱动基因突变的识别”。该提案的目的是检验以下假设：不同种族个体中发生的结肠癌的驱动基因 [CAN 基因] 突变模式不同，反映了这些群体之间疾病流行病学、生活方式和环境暴露在分子水平上的差异。结直肠癌是常见癌症之一，其因种族/民族病因因素而存在显着差异。非裔美国人的结直肠癌发病率和死亡率明显高于白人。肿瘤 CAN 基因突变谱与几乎所有癌症系统中的癌症进展和临床行为直接相关。我们最近鉴定了 140 个 CRC CAN 基因，并能够根据种族传统对 CRC 患者进行分子分层，并利用患者自我声明的身份，使我们处于独特的地位，可以研究种族对这一基本方面的影响癌症生物学。此外，我们还开发出了评估患者血统对个体肿瘤 CAN 基因突变影响的能力。该提案的目的是对来自非裔美国人和白种人的一组匹配的 CRC 中的 140 个 CAN 基因进行测序。这些患者最初将按自我申报的种族进行分层。此外，这些患者将根据每个人的非洲和欧洲血统信息标记进行重新分类。这些研究是由我们小组的许多不同努力促成的。我们建造了一个大型、注释清楚的生物样本库，其中包含过去 20 年在大型医疗中心接受治疗的患者的结肠癌组织样本。这些标本大部分是福尔马林固定石蜡包埋组织 [FFPE]。在过去的几年里，我们致力于开发复杂的方法来提高从 FFPE 材料中提取 DNA 的可靠性。在这些努力的同时，我们开发了基础设施和知识库来支持本提案中设想的高通量测序。这包括购买“下一代”测序仪和雇用教员以进一步扩大我们机构在该领域的专业知识深度。该提案有可能显着增进对种族/族裔倾向对总体癌症和结直肠癌（第二大常见人类癌症）影响的理解。