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Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring.

Abstract：

:In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10-5. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care.

journal_name

Nat Med

journal_title

Nature medicine

authors

Zviran A,Schulman RC,Shah M,Hill STK,Deochand S,Khamnei CC,Maloney D,Patel K,Liao W,Widman AJ,Wong P,Callahan MK,Ha G,Reed S,Rotem D,Frederick D,Sharova T,Miao B,Kim T,Gydush G,Rhoades J,Huang KY,Omans ND,Bo

doi

10.1038/s41591-020-0915-3

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

1114-1124

issue

7

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-020-0915-3

journal_volume

26

pub_type

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