Cell-free DNA TAPS provides multimodal information for early cancer detection

被引：52

作者：

Siejka-Zielinska, Paulina ^{[1
,2
]}

Cheng, Jingfei ^{[1
,2
]}

Jackson, Felix ^{[1
,2
,3
]}

Liu, Yibin ^{[1
,2
,21
]}

Soonawalla, Zahir ^{[4
]}

Reddy, Srikanth ^{[5
]}

Silva, Michael ^{[6
]}

Puta, Luminita ^{[1
]}

McCain, Misti Vanette ^{[7
,8
]}

Culver, Emma L. ^{[9
,10
]}

Bekkali, Noor ^{[11
]}

Schuster-Bockler, Benjamin ^{[1
,12
]}

Palamara, Pier Francesco ^{[13
,14
]}

Mann, Derek ^{[7
,15
,16
]}

Reeves, Helen ^{[7
,8
,17
]}

Barnes, Eleanor ^{[9
,10
]}

Sivakumar, Shivan ^{[18
,19
,20
]}

Song, Chun-Xiao ^{[1
,2
]}

机构：

[1] Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Med, Oxford, England

[2] Univ Oxford, Target Discovery Inst, Nuffield Dept Med, Oxford, England

[3] Univ Oxford, Dept Comp Sci, Oxford, England

[4] Oxford Univ Hosp NHS Fdn Trust, Oxford, England

[5] Churchill Hosp, Oxford Transplant Ctr, Oxford, England

[6] Oxford Univ Hosp NHS Fdn Trust, Dept HPB Surg, Oxford, England

[7] Newcastle Univ, Translat & Clin Res Inst, Med Sch, Newcastle Upon Tyne, Tyne & Wear, England

[8] Newcastle Univ, Ctr Canc, Med Sch, Newcastle Upon Tyne, Tyne & Wear, England

[9] Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg, Oxford, England

[10] Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, Oxford, England

[11] Oxford Univ Hosp NHS Trust, John Radcliffe Hosp, Dept Gastroenterol, Oxford, England

[12] Univ Oxford, Big Data Inst, Oxford, England

[13] Univ Oxford, Dept Stat, Oxford, England

[14] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[15] Newcastle Univ, Fac Med Sci, Biosci Inst, Newcastle Fibrosis Res Grp, Newcastle Upon Tyne, Tyne & Wear, England

[16] Newcastle Univ, Med Sch, Fibrofind, Newcastle Upon Tyne, Tyne & Wear, England

[17] Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Liver Unit, Newcastle Upon Tyne, Tyne & Wear, England

[18] Univ Oxford, Dept Oncol, Oxford, England

[19] Oxford Univ Hosp NHS Fdn Trust, Dept Oncol, Oxford, England

[20] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

[21] Exact Sci Innovat, Innovat Bldg, Oxford OX3 7FZ, England

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 36期

关键词：

HEPATOCELLULAR-CARCINOMA; PANCREATIC-CANCER; PROBLEMATIC REGIONS; GENOME BROWSER; METHYLATION; IDENTIFICATION; DIAGNOSIS; SURVIVAL; PATHWAY; MODELS;

D O I：

10.1126/sciadv.abh0534

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.

引用

页数：11

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