152P - Nanopore sequencing of cfDNA captures key copy number alterations in lung adenocarcinoma: A non-invasive approach for prognosis, therapy, and subtyping

Background

The detection of copy number alterations (CNAs) is an informative molecular layer in the diagnosis, prognosis, and treatment of lung adenocarcinoma. Traditional tissue biopsies are invasive and often impractical. This study investigates the use of nanopore sequencing on circulating cell-free DNA (cfDNA) as a non-invasive, PCR-free method to detect CNAs in lung adenocarcinoma patients.

Methods

Native cfDNA samples from lung adenocarcinoma patients were analysed using low coverage nanopore sequencing (∼ 1- 3 X). Bioinformatics analysis identified CNAs, which were compared to known CNA patterns in tissue samples. Additionally, tumor fractions were estimated to correlate with tumor stage and aggressiveness.

Results

Nanopore sequencing of cfDNA revealed clinically significant and informative CNAs, including amplifications of 1q (MDM4), chromosome 7 (EGFR) as well as deletion of 8p. These alterations closely mirrored the classic CNA patterns observed in lung adenocarcinoma tissue samples, especially in cfDNA samples derived from patients with progressive cancers (i.e. stage 3-4). The analysis also provided tumor fraction estimates, which correlated with tumor stage and aggressiveness.

Conclusions

This study demonstrates that nanopore sequencing of cfDNA can accurately detect CNAs and estimate tumor fractions, offering a non-invasive alternative to tissue biopsies. This approach holds significant potential for real-time cancer monitoring, prognosis prediction, targeted therapy, and precise cancer subtyping. Estimating tumor fractions is also useful for predicting cancer progression and determining future sequencing coverage and planning.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Renovaro Cube.

Disclosure

K. Roohollahi, E. Post, D. Makarawung, F. van Asch: Financial Interests, Institutional, Stocks/Shares: Renovaro Cube. D. Vessies, J. van den Berg: Financial Interests, Personal, Stocks/Shares: Renovaro Cube.