Accurate detection of circulating tumor DNA using nanopore consensus sequencing

被引：29

作者：

Marcozzi, Alessio ^{[1
,2
,3
]}

Jager, Myrthe ^{[1
,2
]}

Elferink, Martin ^{[4
]}

Straver, Roy ^{[1
,2
]}

van Ginkel, Joost H. ^{[5
,6
]}

Peltenburg, Boris ^{[7
,8
]}

Chen, Li-Ting ^{[1
,2
]}

Renkens, Ivo ^{[1
,2
]}

van Kuik, Joyce ^{[5
]}

Terhaard, Chris ^{[7
]}

de Bree, Remco ^{[8
]}

Devriese, Lot A. ^{[9
]}

Willems, Stefan M. ^{[5
,11
]}

Kloosterman, Wigard P. ^{[3
,10
]}

de Ridder, Jeroen ^{[1
,2
,3
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Ctr Mol Med, Utrecht, Netherlands

[2] Univ Utrecht, Univ Med Ctr Utrecht, Oncode Inst, Utrecht, Netherlands

[3] Cyclom, Utrecht, Netherlands

[4] Univ Utrecht, Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands

[5] Univ Utrecht, Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[6] Univ Utrecht, Univ Med Ctr Utrecht, Dept Oral & Maxillofacial Surg, Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, UMC Utrecht Canc Ctr, Dept Radiotherapy, Utrecht, Netherlands

[8] Univ Med Ctr Utrecht, UMC Utrecht Canc Ctr, Dept Head & Neck Surg Oncol, Utrecht, Netherlands

[9] Univ Med Ctr Utrecht, UMC Utrecht Canc Ctr, Dept Med Oncol, Utrecht, Netherlands

[10] Univ Utrecht, Univ Med Ctr Utrecht, Ctr Mol Med, Utrecht, Netherlands

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

来源：

NPJ GENOMIC MEDICINE | 2021年 / 6卷 / 01期

关键词：

BIOPSY; AGE;

D O I：

10.1038/s41525-021-00272-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy similar to 60x, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows.

引用

页数：11

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