Abstract
Pleural mesothelioma (PM) is an aggressive malignancy typically diagnosed at an advanced stage, resulting in poor prognosis. Early detection remains a major clinical challenge. Circulating tumor DNA (ctDNA) analysis offers a promising non-invasive approach, but current strategies rely on patient-specific tumor-informed sequencing, which is a very costly two-step process that limits population-wide screening.
In recent whole-genome sequencing (WGS) studies, we identified the unexpected presence of recurrent structural variant (SV) junctions across independent PM samples. This discovery provides a basis for universal biomarkers, enabling affordable ctDNA testing with potentially high sensitivity. Such an assay could be a game changer in diagnosis of PM.
This project aims to systematically map recurrent SV junctions using published WGS datasets and develop a multiplex cfDNA assay for their detection. Single-molecule molecular inversion probes (smMIPs) will be designed to capture these junctions in a high-throughput format, enabling sensitive and specific detection of SVs in cfDNA. The assay will be validated in PM tissue and plasma samples from PM patients, asbestos-exposed individuals, and healthy volunteers.
By integrating multiple recurrent junctions into a single panel, we aim to establish a tumor-naïve, non-invasive screening tool for early PM detection. Successful implementation could revolutionize clinical practice by enabling accurate diagnosis and screening in at-risk populations.
Researcher(s)
Research team(s)
Project type(s)