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Pathologica
Published

Technical feasibility of a long read, fourth generation sequencing platform in diagnostic profiling of clinical routine samples: a proof-of-concept study

Authors

Domenico Vitale, Lorenzo Colarossi, Gianluca Russo, Claudia Scimone, Domenico Cozzolino, Caterina De Luca, Andrey D Prjibelski, Alla Mikheenko, Cristina Colarossi, Francesco Delli Muti, Francesco Pepe, Lorenzo Memeo, Giancarlo Troncone, Lucia Anna Muscarella, Umberto Malapelle

Abstract

Pathologica. 2026 Apr;118(2):118-125. doi: 10.32074/1591-951X-1936.

ABSTRACT

BACKGROUND: Next generation sequencing (NGS) impacted on clinical algorithm of solid tumor patients. A heterogeneous series of NGS platforms have been implemented in clinical practice but challenging handling procedures, high technical costs, and scant affordability on sequencing diagnostic routine specimens can leave behind some patients who could benefit from target drugs. Here, we sought to evaluate technical feasibility of Oxford Nanopore Technologies (ONT) sequencing accurate identification of tumor-associated molecular alterations, in a pilot series of real-world samples.

METHODS: We developed a technical workflow adapting the SiRe® NGS panel, originally designed for Ion semiconductor sequencing, on MinION platform (Oxford nanopore technologies), a portable, cost effective long read sequencer. The SiRe® panel enables detection of ٥٦٨ clinically actionable somatic mutations across six key genes (EGFR, KRAS, NRAS, BRAF, cKIT, PDGFRα) relevant to targeted therapies in several solid tumors. We implemented a multiplexed assay using pooled and barcoded samples, processed on a single MinION flow cell. Performance was benchmarked from a pilot series of nine FFPE samples against Ion Torrent sequencing data. A single liquid biopsy sample was also analyzed testing accuracy of MinION technology.

RESULTS: The adapted ONT workflow demonstrated high concordance ratei in detecting clinically relevant molecular alterations on short-read fragments, achieving comparable accuracy with standardized second generation NGS platforms on tissue and liquid biopsy samples.

CONCLUSIONS: This proof of concept aimed to integrate ONT sequencing into molecular oncology workflows, providing practical, low-cost, and scalable alternative to conventional NGS platforms. The results support the potential of ONT technology to democratize access to precision oncology, particularly in laboratories with limited resources.

PMID:42157739 | DOI:10.32074/1591-951X-1936

UK DRI Authors