Genomics of Renal Cancer in Patients of African Ancestry
非洲血统患者肾癌的基因组学
基本信息
- 批准号:10648882
- 负责人:
- 金额:$ 26.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-02 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:22qAfricanAfrican ancestryAneuploidyBiologicalBiological FactorsBiologyBlack raceCarrots - dietaryCell LineChromosomesClear CellClear cell renal cell carcinomaClinicalCollaborationsComputer AnalysisCoupledDNA Sequence AlterationDataData SetDiagnostic testsDiseaseDisparityEarly DiagnosisEnvironmental Risk FactorEuropeanEuropean ancestryEventFoundationsGenesGeneticGenome engineeringGenomicsIncidenceKnowledgeMedicineModelingMolecularMutateMutationNeurofibromin 2OncogenesOncogenicOutcomePapillaryPatientsPhenotypePopulationPrognostic MarkerRenal Cell CarcinomaRenal carcinomaReportingResearchSample SizeSamplingSocioeconomic StatusTumor Suppressor GenesVHL geneVHL mutationVariantblack patientchromosome mutationcohortdisparity reductionexome sequencingexperimental studyfunctional genomicsgenome sequencinggenomic datahealth disparityimprovedinsightkidney cellnew therapeutic targetnovelnovel therapeuticspatient populationprecision medicinepublic databaseracial disparityracial populationstructural determinantssurvival disparitytherapeutic targettranscriptome sequencingtumortumorigenesiswhole genome
项目摘要
PROJECT SUMMARY
The outcomes of Black patients are worse than white patients across renal cell carcinoma (RCC) subtypes. Black
patients also suffer higher disease incidence compared to the white patient population, particularly for the
papillary subtype. Environmental and structural factors likely contribute to this disparity; however, there is
evidence suggesting that somatic genomic differences also contribute. Although patients of African (AFR)
ancestry are under-represented in most publicly available databases, decreased VHL gene mutation and
chromosome 3p deletion in clear cell RCC patients of AFR ancestry was observed compared to European (EUR)
ancestry. In our preliminary data with increased sample size, we found NF2 mutations and chromosome 22q
deletion to be more frequent in RCCs from patients of AFR ancestry across subtypes. These preliminary findings
of genomic correlations with ancestry lead us to hypothesize that the survival disparity may be partially explained
by molecular features enriched in tumors from patients of AFR ancestry.
In this project, we will take three parallel approaches to understanding the molecular tumor differences between
patients of AFR and EUR ancestry. In the first aim, we will perform a comprehensive computational analysis of
larger RCC datasets to validate and identify new genomic tumor differences between these two patient
populations. In the second aim, we will functionally characterize the “ancestry-specific” genomic alterations
identified in preliminary studies, including two aneuploidy events - chromosome 3p deletion and chromosome
22q deletion. Lastly, in the third aim, we will move beyond panel and exome sequencing to identify new driver
events, using whole-genome sequencing coupled with RNA-sequencing on tumors from Black patients. The
results from these experiments will lead to new insights about the specific biology of RCC in this patient
population. Our studies will reveal ancestry-associated driver alterations that could not only improve diagnostic
testing for RCC patients of AFR ancestry, but will also identify new therapeutic targets to decrease the disparities
observed in RCC.
项目摘要
在肾细胞癌(RCC)亚型中,黑人患者的结局比白色患者差。黑色
与白色患者群体相比,
乳头状亚型环境和结构因素可能导致这种差异;然而,
有证据表明,体细胞基因组差异也有贡献。非洲患者(AFR)
祖先在大多数公开数据库中代表性不足,VHL基因突变减少,
与欧洲人(EUR)相比,观察到AFR血统的透明细胞RCC患者的染色体3 p缺失
祖先在我们增加样本量的初步数据中,我们发现NF 2突变和染色体22 q
在来自AFR血统的患者的RCC中,缺失在亚型中更常见。这些初步结果
基因组与祖先的相关性使我们假设,生存差异可能部分解释
AFR患者肿瘤中富集的分子特征。
在这个项目中,我们将采取三种平行的方法来了解分子肿瘤的差异,
AFR和EUR血统的患者。在第一个目标中,我们将执行一个全面的计算分析,
更大的RCC数据集,以验证和识别这两名患者之间新的基因组肿瘤差异
人口。在第二个目标中,我们将从功能上描述“祖先特异性”基因组改变
在初步研究中发现,包括两个非整倍性事件-染色体3 p缺失和染色体
22 q缺失。最后,在第三个目标中,我们将超越面板和外显子组测序,以确定新的驱动因素。
事件,使用全基因组测序结合RNA测序对来自黑人患者的肿瘤。的
这些实验的结果将使我们对该患者肾细胞癌的特异性生物学有新的认识
人口我们的研究将揭示与祖先相关的驱动因素改变,不仅可以改善诊断,
检测AFR血统的RCC患者,但也将确定新的治疗靶点,以减少差异
在RCC中观察到。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alison M. Taylor其他文献
Commercialisation and commodification of breastfeeding: video diaries by first-time mothers
- DOI:
10.1186/s13006-020-00264-1 - 发表时间:
2020-05-01 - 期刊:
- 影响因子:2.800
- 作者:
Alison M. Taylor;Jo Alexander;Edwin van Teijlingen;Kath M. Ryan - 通讯作者:
Kath M. Ryan
Ultrastructural organisation of the projection from the superior colliculus to the ventral lateral geniculate nucleus of the rat
大鼠上丘至腹外侧膝状核投射的超微结构组织
- DOI:
- 发表时间:
1987 - 期刊:
- 影响因子:0
- 作者:
Alison M. Taylor;A. Lieberman;London;Gower St;London WClE - 通讯作者:
London WClE
Publisher Correction: Whole-genome doubling confers unique genetic vulnerabilities on tumour cells
出版商更正:全基因组加倍赋予肿瘤细胞独特的遗传脆弱性
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:64.8
- 作者:
Ryan J. Quinton;Amanda DiDomizio;M. Vittoria;K. Kotýnková;Carlos J Ticas;S. Patel;Y. Koga;J. Vakhshoorzadeh;Nicole M Hermance;Taruho S. Kuroda;Neha Parulekar;Alison M. Taylor;Amity L Manning;Joshua D. Campbell;Neil J. Ganem - 通讯作者:
Neil J. Ganem
Modeling Diamond Blackfan anemia in the zebrafish.
斑马鱼钻石黑扇贫血模型。
- DOI:
10.1053/j.seminhematol.2011.02.002 - 发表时间:
2011 - 期刊:
- 影响因子:3.6
- 作者:
Alison M. Taylor;L. Zon - 通讯作者:
L. Zon
Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases
非小细胞肺癌脑转移的单细胞和空间基因组图谱
- DOI:
10.1038/s41591-025-03530-z - 发表时间:
2025-02-27 - 期刊:
- 影响因子:50.000
- 作者:
Somnath Tagore;Lindsay Caprio;Amit Dipak Amin;Kresimir Bestak;Karan Luthria;Edridge D’Souza;Irving Barrera;Johannes C. Melms;Sharon Wu;Sinan Abuzaid;Yiping Wang;Viktoria Jakubikova;Peter Koch;D. Zack Brodtman;Banpreet Bawa;Sachin K. Deshmukh;Leon Ebel;Miguel A. Ibarra-Arellano;Abhinav Jaiswal;Carino Gurjao;Jana Biermann;Neha Shaikh;Priyanka Ramaradj;Yohanna Georgis;Galina G. Lagos;Matthew I. Ehrlich;Patricia Ho;Zachary H. Walsh;Meri Rogava;Michelle Garlin Politis;Devanik Biswas;Azzurra Cottarelli;Nikhil Rizvi;Catherine A. Shu;Benjamin Herzberg;Niroshana Anandasabapathy;George Sledge;Emmanuel Zorn;Peter Canoll;Jeffrey N. Bruce;Naiyer A. Rizvi;Alison M. Taylor;Anjali Saqi;Hanina Hibshoosh;Gary K. Schwartz;Brian S. Henick;Fei Chen;Denis Schapiro;Parin Shah;Benjamin Izar - 通讯作者:
Benjamin Izar
Alison M. Taylor的其他文献
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{{ truncateString('Alison M. Taylor', 18)}}的其他基金
Elucidating the Consequences of Chromosome 3 Arm Aneuploidies in Squamous Cell Carcinoma
阐明鳞状细胞癌中染色体 3 臂非整倍体的后果
- 批准号:
10736206 - 财政年份:2023
- 资助金额:
$ 26.33万 - 项目类别:
Functional Understanding of Chromosome Arm Aneuploidies
染色体臂非整倍体的功能理解
- 批准号:
10684338 - 财政年份:2022
- 资助金额:
$ 26.33万 - 项目类别:
Functional Approaches to Understanding Cancer Aneuploidy: Interrogating the Effects of Chromosome 3p Deletion
了解癌症非整倍性的功能方法:探究染色体 3p 缺失的影响
- 批准号:
10066326 - 财政年份:2020
- 资助金额:
$ 26.33万 - 项目类别:
Functional Approaches to Understanding Cancer Aneuploidy: Interrogating the Effects of Chromosome 3p Deletion
了解癌症非整倍性的功能方法:探究染色体 3p 缺失的影响
- 批准号:
10308011 - 财政年份:2020
- 资助金额:
$ 26.33万 - 项目类别:
Functional Approaches to Understanding Cancer Aneuploidy: Interrogating the Effects of Chromosome 3p Deletion
了解癌症非整倍性的功能方法:探究染色体 3p 缺失的影响
- 批准号:
9720378 - 财政年份:2020
- 资助金额:
$ 26.33万 - 项目类别:
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