Identifying Molecular Subtypes of Head and Neck Cancer in Patients with African Ancestry

鉴定非洲血统患者头颈癌的分子亚型

基本信息

批准号：
10624505
负责人：
Fatemeh Momen Heravi
金额：
$ 1.99万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-07 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10624505
关键词：
Affect African ancestry Age Anatomy Biological Characteristics Clinical DNA Sequence Alteration Data Data Set Development Disease Progression Frequencies Genes Genetic Genetic Transcription Genomics Goals Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Health Services Accessibility Human Papillomavirus Incidence Individual Knowledge Larynx Lead Malignant Neoplasms Methods Modality Molecular Molecular Profiling Molecular Target Mutate Mutation Neoplasm Metastasis Nose Operative Surgical Procedures Oral cavity Oropharyngeal Outcome Pathway Analysis Pathway interactions Patient Self-Report Patients Pattern Pharyngeal structure Population Population Study Precision therapeutics Prognosis Protocols documentation Race Recurrence Reduce health disparities Regulator Genes Research Risk Risk Assessment Risk Factors Role Sample Size Sampling Socioeconomic Status Survival Rate Testing The Cancer Genome Atlas Therapeutic Treatment outcome Universities Work base black patient cancer type clinical prognosis cohort genome sequencing genomic profiles health disparity improved inhibitor large datasets minority patient molecular subtypes molecular targeted therapies novel patient population patient stratification personalized management personalized medicine precision medicine profiles in patients screening social health determinants survival outcome targeted treatment therapeutic target tool transcriptome sequencing transcriptomics treatment planning tumor tumorigenesis whole genome

项目摘要

Project Summary Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer worldwide and is observed in the oral cavity, oropharynx, and larynx. With a 5-year survival rate of fifty percent, precision therapy advances are desperately needed for HNSCC patients. Population-based studies have identified disparities between racial groups in HNSCC treatment and survival, especially for patients with African ancestry. This disparity exists even after controlling for social determinants of health and access to care. The younger incidence of HNSCC in black patients compared to white patients suggests a biological component may be contributing. Genomic and transcriptomic correlations for ancestry have been assessed across cancer and in individual cancer types. However, most of these studies are limited in sample size for HNSCCs, define race based on self-reporting, and have not considered HPV status or anatomical subtype. Because of this, a subset of targetable mutations or pathways could be missing for non-caucasian populations. In the context of genomics research, more accurate tools such as genomic methods must be used when defining and stratifying patients based on race. Here, we will fill this gap in the field by characterizing the molecular features of HNSCC tumors specifically in patients with African ancestry, as defined computationally (rather than by self-reporting). These analyses will give us an unbiased estimate of the relation of ancestry/race and HNSCC molecular features. In addition to DNA alterations, we will also identify transcriptomic changes associated with HNSCC. Pathway analysis of will uncover tumor vulnerabilities in black patients which may be therapeutic targets. Our preliminary analysis identified a higher frequency of MYC amplifications and increased MYC transcriptional activity in HNSCC tumors of patients with African ancestry. In this proposal, we will also assess the utility of two novel MYC inhibitors as a targeted therapy for HNSCC. Taken together, our work will deepen the understanding of HNSCC in patients with African ancestry, with the ultimate goal of developing personalized therapies and reducing health disparities.

项目摘要头颈部鳞状细胞癌（HNSCC）是全球第七大癌症，观察到在口腔中，口咽和喉。精密疗法的5年生存率为50％ HNSCC患者迫切需要。基于人群的研究确定了种族之间的差异 HNSCC治疗和生存的组，特别是对于非洲血统患者。这种差异甚至存在在控制了健康的社会决定因素之后。黑色HNSCC的年轻发病率是黑色的与白人患者相比，患者表明可能有生物成分造成贡献。基因组和祖先的转录组相关性已在癌症和单个癌症类型中进行了评估。但是，这些研究中的大多数在HNSCCs的样本量中受到限制，根据自我报告定义种族，以及尚未考虑HPV状态或解剖亚型。因此，一部分可靶向突变或非高加索人群可能缺少途径。在基因组学研究的背景下，更准确根据种族定义和分层患者，必须使用诸如基因组方法之类的工具。在这里，我们将通过表征专门在HNSCC肿瘤的分子特征来填补该领域的空白非洲血统的患者是计算上定义的（而不是通过自我报告）。这些分析将为我们提供对祖先/种族和HNSCC分子特征关系的无偏估计。除了DNA 改变，我们还将确定与HNSCC相关的转录组变化。遗嘱的途径分析发现黑人患者的肿瘤脆弱性可能是治疗靶标。我们的初步分析确定了较高的MYC扩增频率，并增加了HNSCC肿瘤中MYC转录活性非洲血统的患者。在此提案中，我们还将评估两种新型MYC抑制剂作为一个针对HNSCC的靶向疗法。综上所述，我们的工作将加深对非洲血统患者HNSCC的理解，开发个性化疗法并减少健康差异的最终目标。