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癌症基因组图谱中非洲裔美国人和白人患者肿瘤之间的差异选择性 RNA 剪接和转录事件。

Differential alternative RNA splicing and transcription events between tumors from African American and White patients in The Cancer Genome Atlas.

机构信息

Duke Cancer Institute, Duke University School of Medicine, Durham, NC, 27710, USA.

Duke Cancer Institute, Duke University School of Medicine, Durham, NC, 27710, USA; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, 27710, USA.

出版信息

Genomics. 2021 May;113(3):1234-1246. doi: 10.1016/j.ygeno.2021.02.020. Epub 2021 Mar 8.

Abstract

Individuals of African ancestry suffer disproportionally from higher incidence, aggressiveness, and mortality for particular cancers. This disparity likely results from an interplay among differences in multiple determinants of health, including differences in tumor biology. We used The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA aggregate expression datasets and identified differential alternative RNA splicing and transcription events (ARS/T) in cancers between self-identified African American (AA) and White (W) patients. We found that retained intron events were enriched among race-related ARS/T. In addition, on average, 12% of the most highly ranked race-related ARS/T overlapped between any two analyzed cancers. Moreover, the genes undergoing race-related ARS/T functioned in cancer-promoting pathways, and a number of race-related ARS/T were associated with patient survival. We built a web-application, CanSplice, to mine genomic datasets by self-identified race. The race-related targets have the potential to aid in the development of new biomarkers and therapeutics to mitigate cancer disparity.

摘要

非洲裔个体罹患某些癌症的发病率更高、侵袭性更强且死亡率更高。这种差异可能是多种健康决定因素相互作用的结果,包括肿瘤生物学方面的差异。我们使用癌症基因组图谱(TCGA)剪接测序和 TCGA 综合表达数据集,在自我认定的非裔美国(AA)和白人(W)患者的癌症中确定了差异的选择性 RNA 剪接和转录事件(ARS/T)。我们发现,保留内含子事件在与种族相关的 ARS/T 中富集。此外,平均而言,在任何两个分析的癌症之间,排名最高的与种族相关的 ARS/T 中有 12%重叠。此外,发生与种族相关的 ARS/T 的基因在促进癌症的途径中发挥作用,许多与种族相关的 ARS/T 与患者的生存有关。我们构建了一个名为 CanSplice 的网络应用程序,通过自我认定的种族来挖掘基因组数据集。这些与种族相关的靶标有可能帮助开发新的生物标志物和治疗方法,以减轻癌症的差异。

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