Deciphering Germline and Somatic Genomic Landscape of Gliomas in Black and Hispanic Minority Groups

解读黑人和西班牙裔少数群体胶质瘤的种系和体细胞基因组景观

基本信息

批准号：
10476420
负责人：
Jason Huse
金额：
$ 43.06万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10476420
关键词：
19q Accounting Address Affect African Age Behavior Bioinformatics Biology Black Populations Black race Cancer Biology Case-Control Studies Clinical Clinical Data Collaborations DNA Data Development Disease Disease Progression East Asian Ethnic Origin Ethnic group European Exhibits Formalin Foundations Genetic Genetic Polymorphism Genomics Glioblastoma Glioma Heterogeneity Hispanic Hispanic Populations Incidence International Investigation Knowledge Light Malignant Glioma Malignant neoplasm of brain Measures Methodology Minority Minority Groups Modeling Molecular Molecular Epidemiology Molecular Profiling Mutation Outcome Pathogenesis Pathogenicity Patients Pattern Performance Predisposition Recording of previous events Research Resources Risk Sampling Single Nucleotide Polymorphism Site Source Specific qualifier value Specimen Stratification Subgroup The Cancer Genome Atlas Tumor Subtype Underrepresented Minority Variant Work base clinical prognosis clinically relevant cohort comparative design epidemiologic data experience genome wide association study genomic data genomic locus improved innovation insight minority patient mutant neuro-oncology neuropathology next generation sequencing patient population personalized management prospective racial and ethnic recruit therapeutic development treatment optimization treatment strategy tumor

项目摘要

SUMMARY: PROJECT 3 Recent genomic profiling, including that of the Cancer Genome Atlas, has greatly clarified the molecular foundations of malignant glioma. However, most of the sample sets employed in these groundbreaking studies were derived from White or East Asian patients. Very little is currently known about the somatic and germline landscapes of gliomas in Black or Hispanic populations. Moreover, significant differences in the annual incidence and clinical performance of gliomas in these minorities relative to those of Whites strongly suggests that fundamental and clinically-relevant genetic distinctions exist between the groups. Consistent with this conjecture, we recently found that patterns of germline single nucleotide polymorphisms (SNPs) differentially associated with glioma by ethnic group and that Blacks and Hispanics with a higher level of White ancestry had a greater risk for glioma development than those with lower levels. We also identified a unique set of SNPs, distinct from glioma-associated SNPs in Whites, that appear to confer glioma susceptibility in Blacks and Hispanics. These findings indicate that a larger study, probing both somatic and germline molecular profiles exclusively in Black and Hispanic patients, would bridge crucial knowledge gaps, setting the stage for more optimized, individualized patient management. The central hypothesis of this proposal is that distinct genetic features, germline and somatic, in Blacks and Hispanics influence risk and clinical prognosis in IDH-mutant and IDH-wild type glioma subgroups. We will combine germline SNP data with extensive genomic profiling in case-matched tumors from the largest, clinically-annotated minority patient cohort assembled to date. Our specific aims will 1) characterize the genomic landscape of glioma in Black and Hispanic patients, 2) determine the extent to which ethnic composition in Blacks and Hispanics correlates with disease-defining molecular alterations, and 3) evaluate the extent to which germline and somatic variation in Blacks and Hispanics impacts clinical outcome. Our work will clarify the somatic and germline genetics of glioma in Black and Hispanic populations and in doing so, address a major knowledge gap in the field. We will also establish robust correlations between ancestry-associated germline genetics, molecularly-specified glioma subclasses, and clinical outcome, providing insights into the mechanisms by which gliomas arise and behave in patient populations of differing ethnicity. These findings should both inform therapeutic development and facilitate the design of optimized patient management.

摘要：项目3 最近的基因组分析，包括癌症基因组图集的基因组分析，已大大阐明了分子恶性神经胶质瘤的基础。但是，这些开创性研究中采用的大多数样本集源自白人或东亚患者。目前对躯体和种系知之甚少黑色或西班牙裔人群中神经胶质瘤的景观。此外，年发病率的显着差异与白人相对于白人的胶质瘤的临床表现强烈表明两组之间存在基本和临床上与临床相关的遗传区别。与这个猜想一致我们最近发现，种系单核苷酸多态性（SNP）的模式差异相关与种族群体的神经瘤以及黑人血统更高的黑人和西班牙裔的人有更大的胶质瘤发育的风险比水平较低的风险。我们还确定了一套独特的SNP，不同于与胶质瘤相关的白人中的SNP，这些SNP似乎赋予黑人和西班牙裔的神经胶质瘤敏感性。这些研究结果表明，一项较大的研究，仅以黑色探测躯体和种系分子曲线和西班牙裔患者将弥合关键的知识差距，为更优化，个性化的患者管理。该提议的中心假设是不同的遗传特征，种系和在黑人和西班牙裔中，体细胞影响IDH突变和IDH野生型胶质瘤的风险和临床预后亚组。我们将在病例匹配的肿瘤中结合种系SNP数据与广泛的基因组分析迄今为止，最大的，临床上注销的少数族裔患者队列组装。我们的具体目的会1）黑人和西班牙裔患者神经胶质瘤的基因组景观，2）确定种族的程度黑人和西班牙裔的组成与定义疾病的分子改变相关，3）评估黑人和西班牙裔的种系和躯体变异的程度影响临床结果。我们的工作将阐明黑人和西班牙裔人群中神经胶质瘤的躯体和种系遗传学，并在此解决该领域的主要知识差距。我们还将在祖先相关之间建立牢固的相关性种系遗传学，分子指定的神经胶质瘤亚类和临床结局，为您提供了见解神经胶质瘤在不同种族不同的患者种群中产生和行为的机制。这些发现应既应该为治疗性开发提供信息，又可以促进设计优化的患者管理的设计。