University of South Florida, USF Health Morsani College of Medicine, Tampa, FL.
Department of Pediatrics, University of Washington, Seattle, WA.
JCO Precis Oncol. 2024 Oct;8:e2400223. doi: 10.1200/PO.24.00223. Epub 2024 Oct 24.
In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC.
Using 416 LUSC tumor samples in the Cancer Genome Atlas (TCGA), we assessed genomic and transcriptomic profiles by ancestry. We replicated our analyses in pan-cancer data from TCGA, the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE), and Columbia University Medical Center.
We found increased amplification, LUSC-specific enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the locus in TCGA. We also found a significant correlation between chr8q and AFR ancestry in multiple cancer types and pan-cancer in TCGA. Similarly, in a pan-cancer subset of AACR GENIE data, we found a significant correlation between chr8q gain and race.
Together, our data suggest that ancestry may influence amplification of not only but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti- therapeutic approaches.
在肺鳞状细胞癌（LUSC）中，黑人患者的发病率明显高于白人患者，总生存率低于白人患者。尽管社会经济因素可能导致这种生存差异，但 LUSC 的基因组因素尚未阐明。
我们使用癌症基因组图谱（TCGA）中的 416 个 LUSC 肿瘤样本，通过祖先评估基因组和转录组谱。我们在 TCGA、美国癌症研究协会（AACR）基因组证据肿瘤信息交换（GENIE）和哥伦比亚大学医学中心的泛癌症数据中复制了我们的分析。
我们发现，在 TCGA 的 LUSC 中，扩增、LUSC 特异性增强子扩增和染色体臂 8q（chr8q）获得与遗传 AFR（非洲）祖先显著相关。此外，在 AFR 样本中， 靶基因的表达明显富集。局部祖先分析确定了 TCGA 中 chr8q 获得与 位点的 AFR 祖先之间的相关性。我们还在 TCGA 的多个癌症类型和泛癌症中发现了 chr8q 与 AFR 祖先之间的显著相关性。同样，在 AACR GENIE 数据的泛癌症亚集中，我们发现 chr8q 增益与种族之间存在显著相关性。
总之，我们的数据表明，祖先可能不仅影响 扩增，还可能影响其增强子在 LUSC 中的作用。它们还表明遗传祖先在癌症中 chr8q 非整倍体中的作用。这些研究进一步定义和扩大了可能受益于未来抗 治疗方法的患者群体。
