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Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

By Xiaoyu Liu, Lingxiao Liu, Yuan Ji, Changyu Li, Tao Wei, Xuerong Yang, Yuefang Zhang, Xuyu Cai, Ting Yang, Yangbin Gao, Weihong Xu, Shengxiang Rao, Dayong Jin, Wenhui Lou, Zilong Qiu, Xiaolin Wang

Posted 04 Dec 2018
bioRxiv DOI: 10.1101/482745 (published DOI: 10.1016/j.ebiom.2019.02.010)

Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical settings, but with significant bias towards late-stage cancers. Although recent studies have discussed the diverse and degraded nature of cfDNA molecules, little is known about its impact on the practice of cfDNA analysis. Here we reported a new targeted sequencing by combining single-strand library preparation and target capture (SLHC-seq). By applying the new technology in plasma cfDNA from pancreatic cancer patients, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumor DNA detection. Most importantly, we found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based early detection of pancreatic cancer. Collectively, the new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy.

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