美国纪念斯隆凯特琳癌症中心Jian Carrot-Zhang课题组发现，非洲(AFR)血统的肿瘤测序揭示了常见癌症临床相关改变的差异。相关论文发表在2023年10月26日出版的《癌细胞》杂志上。

他们利用两个大型基因组队列来研究六种常见癌症中基因组改变与AFR血统之间的关系。在肺癌、乳腺癌和前列腺癌中观察到MYC扩增与AFR祖先的富集，在结直肠癌和胰腺癌中观察到BRAF改变的减少。在肺癌中，可操作的改变存在差异，例如KRAS G12C和EGFR L858R的缺失，以及ROS1与AFR祖先融合的富集。

有趣的是，在肺癌中，KRAS突变在具有AFR血统的吸烟者和非吸烟者中都不常见，而TP53突变与AFR血统的关联仅在吸烟者中可见，这表明遗传-环境相互作用改变了驱动率。他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。

据悉，来自AFR血统患者的癌症基因组在临床研究中研究很少。

附：英文原文

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

Author: 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, Jian Carrot-Zhang

Issue&Volume: 2023-10-26

Abstract: 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.

DOI: 10.1016/j.ccell.2023.10.003

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00359-8