Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context
Background: 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...
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Format: | Article |
Language: | English |
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Elsevier
2019-03-01
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Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419300830 |
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doaj-19530995874f4e48b6578db15f4dcab8 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoyu Liu Lingxiao Liu Yuan Ji Changyu Li Tao Wei Xuerong Yang Yuefang Zhang Xuyu Cai Yangbin Gao Weihong Xu Shengxiang Rao Dayong Jin Wenhui Lou Zilong Qiu Xiaolin Wang |
spellingShingle |
Xiaoyu Liu Lingxiao Liu Yuan Ji Changyu Li Tao Wei Xuerong Yang Yuefang Zhang Xuyu Cai Yangbin Gao Weihong Xu Shengxiang Rao Dayong Jin Wenhui Lou Zilong Qiu Xiaolin Wang Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context EBioMedicine |
author_facet |
Xiaoyu Liu Lingxiao Liu Yuan Ji Changyu Li Tao Wei Xuerong Yang Yuefang Zhang Xuyu Cai Yangbin Gao Weihong Xu Shengxiang Rao Dayong Jin Wenhui Lou Zilong Qiu Xiaolin Wang |
author_sort |
Xiaoyu Liu |
title |
Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context |
title_short |
Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context |
title_full |
Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context |
title_fullStr |
Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context |
title_full_unstemmed |
Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in context |
title_sort |
enrichment of short mutant cell-free dna fragments enhanced detection of pancreatic cancerresearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-03-01 |
description |
Background: 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. Methods: We developed single-strand library preparation and hybrid-capture-based cfDNA sequencing (SLHC-seq) to analysis degraded cfDNA fragments. Next we used SLHC-seq to perform cfDNA profiling in 112 pancreatic cancer patients, and the results were compared with 13 previous reports. Extensive analysis was performed in terms of cfDNA fragments to explore the reasons for higher detection rate of KRAS mutations in the circulation of pancreatic cancers. Findings: By applying the new approach, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. 791 cancer-specific mutations were detected in plasma of 88% patients with KRAS hotspots detected in 70% of all patients. Only 8 mutations were detected in 28 healthy controls without any known oncogenic or truncating alleles. cfDNA profiling by SLHC-seq was largely consistent with results of tissue-based sequencing. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumour DNA detection. Interpretation: We found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based detection of pancreatic cancer. The new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy. Keywords: Pancreatic cancer, Cell-free DNA, Fragmentation, Tissue biopsy, Diagnosis and prognosis |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419300830 |
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doaj-19530995874f4e48b6578db15f4dcab82020-11-25T02:13:00ZengElsevierEBioMedicine2352-39642019-03-0141345356Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancerResearch in contextXiaoyu Liu0Lingxiao Liu1Yuan Ji2Changyu Li3Tao Wei4Xuerong Yang5Yuefang Zhang6Xuyu Cai7Yangbin Gao8Weihong Xu9Shengxiang Rao10Dayong Jin11Wenhui Lou12Zilong Qiu13Xiaolin Wang14Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China; Institute of Neuroscience, State Kay Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, ChinaDepartment of Pathology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, ChinaDepartment of Radiology, Shuguang Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Neuroscience, State Kay Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, ChinaPrecision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaQihan Bio Inc., Hangzhou, Zhejiang, ChinaStanford Genome Technology Center, Palo Alto, CA, USADepartment of Radiology, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China; Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China; Correspondence to: W. Lou, Department of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China.Institute of Neuroscience, State Kay Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; Corresponding author.Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China; Correspondence to: X. Wang, Department of Interventional Radiology, Zhongshan Hospital Fudan University, Shanghai, China.Background: 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. Methods: We developed single-strand library preparation and hybrid-capture-based cfDNA sequencing (SLHC-seq) to analysis degraded cfDNA fragments. Next we used SLHC-seq to perform cfDNA profiling in 112 pancreatic cancer patients, and the results were compared with 13 previous reports. Extensive analysis was performed in terms of cfDNA fragments to explore the reasons for higher detection rate of KRAS mutations in the circulation of pancreatic cancers. Findings: By applying the new approach, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. 791 cancer-specific mutations were detected in plasma of 88% patients with KRAS hotspots detected in 70% of all patients. Only 8 mutations were detected in 28 healthy controls without any known oncogenic or truncating alleles. cfDNA profiling by SLHC-seq was largely consistent with results of tissue-based sequencing. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumour DNA detection. Interpretation: We found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based detection of pancreatic cancer. The new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy. Keywords: Pancreatic cancer, Cell-free DNA, Fragmentation, Tissue biopsy, Diagnosis and prognosishttp://www.sciencedirect.com/science/article/pii/S2352396419300830 |