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

项目摘要 头颈部鳞状细胞癌（HNSCC）是世界上第7大常见癌症， 在口腔、口咽和喉部。随着5年生存率的50%，精确治疗的进步 是HNSCC患者迫切需要的。基于人口的研究发现， 在HNSCC治疗和生存组，特别是非洲血统的患者。这种差异甚至存在于 在控制了健康和获得保健的社会决定因素之后。黑人中HNSCC的年轻发病率 患者与白色患者相比，表明生物成分可能起作用。基因组和 已经在癌症和个体癌症类型中评估了祖先的转录组学相关性。 然而，这些研究中的大多数都局限于HNSCC的样本量，基于自我报告定义种族， 没有考虑HPV状态或解剖亚型。正因为如此，一个可靶向突变的子集或 非高加索人可能缺少这种途径。在基因组学研究的背景下， 在根据种族对患者进行定义和分层时，必须使用基因组方法等工具。 在这里，我们将填补这一空白领域的特点HNSCC肿瘤的分子特征，特别是在 通过计算（而不是自我报告）定义的非洲血统患者。这些分析将 给我们一个无偏估计的关系，血统/种族和HNSCC分子特征。除了DNA 此外，我们还将鉴定与HNSCC相关的转录组学变化。意志的路径分析 发现黑人患者的肿瘤脆弱性，这可能是治疗目标。我们初步分析 在HNSCC肿瘤中发现了更高频率的MYC扩增和增加的MYC转录活性 有非洲血统的病人。在这项提案中，我们还将评估两种新型MYC抑制剂作为治疗药物的效用。 HNSCC的靶向治疗 总之，我们的工作将加深对非洲血统患者HNSCC的理解， 最终目标是开发个性化治疗和减少健康差距。

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.