深度測序揭示血漿循環遊離DNA變體的來源
作者：
小柯機器人發布時間：2019/11/26 15:11:18
美國紀念斯隆-凱特琳癌症中心Jorge S. Reis-Filho研究團隊利用深度測序揭示出血漿循環中游離DNA（cfDNA）變異的來源。相關論文於2019年11月25日在線發表於國際學術期刊《自然—醫學》。
研究人員在對124例轉移性癌症患者以及匹配的腫瘤組織活檢和47例無癌症的對照的前瞻性研究中，確定了cfDNA和匹配的白細胞DNA的強度測序測定技術的可行性，該測定涵蓋了較大的基因組區域（508個基因；2兆鹼基；> 60000倍原始深度）。
該方法顯示出高靈敏度和特異性，可以從頭檢測腫瘤來源的突變，並推斷出cfDNA中鑑定的腫瘤突變負擔、微衛星不穩定性、突變特徵和體細胞突變的來源。絕大多數cfDNA突變（對照組為81.6％，癌症患者為53.2％）具有與克隆性造血一致的特徵。
cfDNA測序方法揭示了克隆性造血是一種普遍的生物學現象，並強調了匹配的cfDNA-白細胞測序對於準確解釋變異的重要性。
據了解，在血漿循環cfDNA中準確鑑定腫瘤來源的體細胞變異體需要了解不同生物區域對cfDNA庫的影響。
附：英文原文
Title: High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants
Author: Pedram Razavi, Bob T. Li, David N. Brown, Byoungsok Jung, Earl Hubbell, Ronglai Shen, Wassim Abida, Krishna Juluru, Ino De Bruijn, Chenlu Hou, Oliver Venn, Raymond Lim, Aseem Anand, Tara Maddala, Sante Gnerre, Ravi Vijaya Satya, Qinwen Liu, Ling Shen, Nicholas Eattock, Jeanne Yue, Alexander W. Blocker, Mark Lee, Amy Sehnert, Hui Xu, Megan P. Hall, Angie Santiago-Zayas, William F. Novotny, James M. Isbell, Valerie W. Rusch, George Plitas, Alexandra S. Heerdt, Marc Ladanyi, David M. Hyman, David R. Jones, Monica Morrow, Gregory J. Riely, Howard I. Scher, Charles M. Rudin, Mark E. Robson, Luis A. Diaz, David B. Solit, Alexander M. Aravanis, Jorge S. Reis-Filho
Issue&Volume: 2019-11-25
Abstract: Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white blood cell DNA covering a large genomic region (508 genes; 2megabases; >60,000× raw depth) in a prospective study of 124 patients with metastatic cancer, with contemporaneous matched tumor tissue biopsies, and 47 controls without cancer. The assay displayed high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in patients with cancer) had features consistent with clonal hematopoiesis. This cfDNA sequencing approach revealed that clonal hematopoiesis constitutes a pervasive biological phenomenon, emphasizing the importance of matched cfDNA–white blood cell sequencing for accurate variant interpretation.
DOI: 10.1038/s41591-019-0652-7
Source: https://www.nature.com/articles/s41591-019-0652-7