We present a highly sensitive, low-cost approach for detecting lung cancer and monitoring response to therapy, based on sequencing-free detection of methylation biomarkers in cell-free DNA. An engineered methyltransferase is used to fluorescently label CpG sites. When applied to bisulfite-treated, PCR-amplified cell-free DNA, fluorescent reporters attach to all originally methylated sites, which can then be read on a standard hybridization microarray. In a proof-of-concept study involving 60 blinded participants, we distinguished cancer patients from healthy individuals with both sensitivity and specificity exceeding 90 %.

The IP for this technology has been licensed to a newly formed spinout company, JaxBio LTD. YE is a founder and holds equity in the company, AA is a scientific consultant to the company, YM and NG are currently employed by the company.

This was funded by the European Research Council consolidator grant [grant number 817811]; Israel Science Foundation [grant number 771/21]

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional Review Board (IRB) of Nazareth Hospital EMMS gave ethical approval for this work Approval number 37-22-EMMS

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Yes

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Yes

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Yes

All data produced in the present study are available upon reasonable request to the authors