文章：

利用无细胞RNA中的零编码序列进行癌症早期检测

Utilizing nullomers in cell-free RNA for early cancer detection 

原文发布日期：2024-02-14 

英文摘要：

Early detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome. We also identify nullomer emerging mutational hotspots within tumor genes. Finally, we provide evidence for the identification of nullomers in cell-free RNA from peripheral blood samples, enabling detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99. 

摘要翻译： 

癌症的早期发现能显著改善患者预后，但目前仍缺乏高灵敏度与高特异性的癌症诊断生物标志物。空位体（nullomer）是指人类基因组中不存在、但因癌症体细胞突变而可能出现的最短序列。我们通过对10,000多例匹配的肿瘤-正常组织全外显子组测序样本进行分析，揭示了空位体在基因组外显子区域的产生规律，并确定了肿瘤基因中空位体产生的突变热点区域。最后，我们通过外周血样本中的游离RNA成功鉴定了空位体，实现了对多种肿瘤类型的检测。我们开发的多项肿瘤分类模型曲线下面积（AUC）均超过0.9，其中肝细胞癌分类器的AUC更达到0.99以上。

原文链接：

Utilizing nullomers in cell-free RNA for early cancer detection