Jiang Peiyong, Sun Kun, Peng Wenlei, Cheng Suk Hang, Ni Meng, Yeung Philip C, Heung Macy M S, Xie Tingting, Shang Huimin, Zhou Ze, Chan Rebecca W Y, Wong John, Wong Vincent W S, Poon Liona C, Leung Tak Yeung, Lam W K Jacky, Chan Jason Y K, Chan Henry L Y, Chan K C Allen, Chiu Rossa W K, Lo Y M Dennis
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
Cancer Discov. 2020 May;10(5):664-673. doi: 10.1158/2159-8290.CD-19-0622. Epub 2020 Feb 28.
Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring. SIGNIFICANCE: Plasma DNA molecules originating from the liver, HCC and other cancers, placenta, and hematopoietic cells each harbor a set of characteristic plasma DNA end motifs. Such markers carry tissue-of-origin information and represent a new class of biomarkers in the nascent field of fragmentomics..
血浆DNA片段组学是一个新兴的研究领域，涵盖血浆DNA大小、端点和核小体足迹。在本研究中，我们发现肝细胞癌（HCC）患者血浆DNA末端基序的多样性显著增加。与无HCC的患者相比，HCC患者表现出4聚体末端基序的偏好模式。特别是，HCC患者血浆DNA基序CCCA的丰度远低于无HCC的受试者。在其他癌症类型的患者中也观察到异常的末端基序，包括结直肠癌、肺癌、鼻咽癌和头颈部鳞状细胞癌。我们进一步观察到，源自同一器官（如肝脏、胎盘和造血细胞）的血浆DNA末端基序谱通常聚集在一起。因此，末端基序谱可作为肿瘤学液体活检、无创产前检测和移植监测的一类生物标志物。意义：源自肝脏、HCC和其他癌症、胎盘和造血细胞的血浆DNA分子各自具有一组特征性的血浆DNA末端基序。这些标志物携带组织起源信息，代表了片段组学这一新兴领域中的一类新型生物标志物。
