Amplification of MYC and Its Enhancer Correlates With Genetic Ancestry in Lung Squamous Cell Carcinoma.

IF 5.3 2区 医学 Q1 ONCOLOGY
JCO precision oncology Pub Date : 2024-10-01 Epub Date: 2024-10-24 DOI:10.1200/PO.24.00223
Sejal Jain, Xuechun Bai, Samyukta Mallick, Branden Kinghorn, Benjamin May, Alexandria G Yao, Diane Allen-Gipson, Xiaoyang Zhang, Brian S Henick, Fatemeh Momen-Heravi, Jian Carrot-Zhang, Alison M Taylor
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Abstract

Purpose: 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.

Methods: 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.

Results: We found increased MYC amplification, LUSC-specific MYC enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of MYC target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the MYC 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.

Conclusion: Together, our data suggest that ancestry may influence amplification of not only MYC 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-MYC therapeutic approaches.

肺鳞状细胞癌中 MYC 及其增强子的扩增与遗传血统有关。
目的: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,但总体生存率却低于白人患者。虽然社会经济因素可能是造成这种生存差异的原因之一,但肺鳞状细胞癌的基因组因素尚未得到阐明:我们利用癌症基因组图谱(TCGA)中的416个LUSC肿瘤样本,评估了不同血统的基因组和转录组特征。我们在TCGA、美国癌症研究协会(AACR)基因组学证据肿瘤信息交换中心(GENIE)和哥伦比亚大学医学中心的泛癌症数据中重复了我们的分析:结果:我们发现,在TCGA中,MYC扩增增加、LUSC特异性MYC增强子扩增和染色体臂8q(chr8q)增益与LUSC的遗传AFR(非洲)血统显著相关。此外,MYC靶基因的表达在非洲裔样本中明显富集。本地祖先分析发现,在 TCGA 的 MYC 基因座上,chr8q 增益与非洲裔祖先相关。我们还发现,在 TCGA 的多种癌症类型和泛癌症中,chr8q 与 AFR 祖先之间存在明显的相关性。同样,在 AACR GENIE 数据的泛癌症子集中,我们也发现了 chr8q 增益与种族之间的显著相关性:总之,我们的数据表明,祖先不仅可能影响 MYC 的扩增,还可能影响其在 LUSC 中的增强子。这些数据还表明,遗传血统在癌症的 chr8q 非整倍体中起着一定的作用。这些研究进一步确定并扩大了未来抗 MYC 治疗方法的受益患者范围。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.10
自引率
4.30%
发文量
363
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