透明细胞肾细胞癌分子亚型在非洲和欧洲遗传相似性群体中有所不同。

IF 2 Q3 ONCOLOGY

Cancer research communications Pub Date : 2025-05-01 DOI:10.1158/2767-9764.CRC-24-0624

Roy Elias, Thomas Nirschl, Michael Rezaee, Anirudh Yerrapragada, Shirley Wang, Joseph Cheaib, Ridwan Alam, Sunil Patel, Yuezhou Jing, Mohamad Allaf, David McKean, Alison P Klein, Elana J Fertig, Ezra Baraban, Yasser Ged, Srinivasan Yegnasubramanian, Nirmish Singla

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引用次数: 0

摘要

相对于白人(W)个体，自我报告的黑人(B)个体在透明细胞肾细胞癌（ccRCC）的分子研究中仍然代表性不足。我们对59例因局部ccRCC而行肾切除术的匹配B和W患者的配对肿瘤和正常样本进行了全外显子组和转录组测序，通过估计的遗传相似性比较了与非洲（AFR）和欧洲（EUR） 1000基因组组的分子差异。我们用倾向匹配的TCGA子集验证了我们的发现，最终产生254例患者（79例AFR， 175欧元），基线临床变量相似。VHL突变频率存在显著差异(AFR: 23.4%, EUR: 57.5%；FDR = 0.0029)和染色体3p缺失(AFR: 59.2%, EUR: 82.6%；罗斯福 = 0.086)。转录组学分析鉴定出34个与遗传相似性相关的基因，基因集富集显示炎症（干扰素γ / α、同种异体移植排斥）、增殖（E2F靶点、G2M检查点）和代谢（胆酸、脂肪酸、糖酵解、MTORC1、过氧化物酶体）途径在EUR中富集。我们还观察到ccRCC分子亚型分布的差异，“增生性”和“血管/基质”亚型在AFR中更常见（p = 0.018）。重要的是，不同的亚型隶属关系解释了大多数群体水平的差异。这些结果将EUR和AFR的遗传相似性与不同的ccRCC分子亚型联系起来，强调了分子分类器在疾病分层中的重要性，以及在分子研究中纳入不同人群以提高我们对ccRCC的理解和治疗的必要性。

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Clear-Cell Renal Cell Carcinoma Molecular Subtypes Differ by African and European Genetic Similarity.

Significance: Our study shows that AFR genetic similarity correlates with distinct ccRCC molecular subtypes. Further research is needed to disentangle environmental and genetic influences. Identifying these differences underscores the critical importance of including racially and ethnically diverse populations in cancer research to ensure more equitable and sustainable outcomes worldwide for all patients.

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Cancer research communications

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