肿瘤测序揭示了非洲血统在常见癌症中临床相关改变的差异

2023-11-15 10:03

在肺癌、乳腺癌和前列腺癌中观察到跨癌类型的关联，如MYC扩增富集与AFR血统有关，以及BRAF改变的缺失。

SCI

11 November 2023

Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers

(Cancer Cell, IF: 50.3)

Evelyn Jiagge, Dexter X. Jin, Justin Y. Newberg, Tomin Perea-Chamblee, Kelly R. Pekala, Christopher Fong, Michele Waters, David Ma, Yvonne Dei-Adomakoh, Gilles Erb, Kanika S. Arora, Sophia L. Maund, Njoki Njiraini, Atara Ntekim, Susie Kim, Xuechun Bai, Marlene Thomas, Ronwyn van Eeden, Priti Hegde, Justin Jee, Debyani Chakravarty, Nikolaus Schultz, Michael F. Berger, Garrett M. Frampton, Ethan S. Sokol, and Jian Carrot-Zhang
CORRESPONDENCE TO: ejiagge1@hfhs.org (E.J.), djin@foundationmedicine.com (D.X.J.), carrotj@mskcc.org (J.C.-Z.)

SUMMARY 摘要

Cancer genomes from patients with African (AFR) ancestry have been poorly studied in clinical research. We leverage two large genomic cohorts to investigate the relationship between genomic alterations and AFR ancestry in six common cancers. Cross-cancer type associations, such as an enrichment of MYC amplification with AFR ancestry in lung, breast, and prostate cancers, and depletion of BRAF alterations are observed in colorectal and pancreatic cancers. There are differences in actionable alterations, such as depletion of KRAS G12C and EGFR L858R, and enrichment of ROS1 fusion with AFR ancestry in lung cancers. Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.

具有非洲（AFR）血统患者的癌症基因组在临床研究中研究不足。我们利用两个大的基因组队列来研究六种常见癌症的基因组改变和AFR血统之间的关系。在肺癌、乳腺癌和前列腺癌中观察到跨癌类型的关联，如MYC扩增富集与AFR血统有关，以及BRAF改变的缺失。在可操作的改变方面存在差异，例如KRAS G12C和EGFR L858R的缺失，以及肺癌中与AFR血统相关的ROS1的富集。有趣的是，在肺癌中，KRAS突变在有AFR血统的吸烟者和非吸烟者中都不太常见，而TP53突变与AFR血统之间的关联仅在吸烟者中可见，这表明存在血统与环境的相互作用改变了驱动率。我们的研究强调了在药物开发和生物标志物发现中增加AFR血统患者代表性的必要性。