Non-invasive multi-cancer detection using DNA hypomethylation of LINE-1 retrotransposons - Institut Curie
Article Dans Une Revue Clinical Cancer Research Année : 2024

Non-invasive multi-cancer detection using DNA hypomethylation of LINE-1 retrotransposons

Maryam Heidary
Caroline Hego
Aurore Rampanou
Constance Lamy
Maud Kamal
Christophe Le Tourneau
Mathieu Séné
Ivan Bièche
Cecile Reyes
David Gentien
Marc‐henri Stern
Olivier Lantz
Luc Cabel
Jean-Yves Pierga
François-Clément Bidard

Résumé

Purpose: The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. Experimental design: We implemented a new highly sensitive strategy to detect base-pair resolution methylation patterns from plasma DNA and assessed the potential of hypomethylation of LINE-1 retrotransposons as a non-invasive multi-cancer detection biomarker. The DIAMOND (Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA) method targets 30-40,000 young L1 scattered throughout the genome, covering about 100,000 CpG sites and is based on a reference-free analysis pipeline. Results: Resulting machine learning-based classifiers showed powerful correct classification rates discriminating healthy and tumor plasmas from 6 types of cancers (colorectal, breast, lung, ovarian, gastric cancers and uveal melanoma including localized stages) in two independent cohorts (AUC = 88% to 100%, N = 747). DIAMOND can also be used to perform copy number alterations (CNA) analysis which improves cancer detection. Conclusions: This should lead to the development of more efficient non-invasive diagnostic tests adapted to all cancer patients, based on the universality of these factors.

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Cancer
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Dates et versions

hal-04830936 , version 1 (07-01-2025)

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Marc Michel, Maryam Heidary, Anissa Mechri, Kevin da Silva, Marine Gorse, et al.. Non-invasive multi-cancer detection using DNA hypomethylation of LINE-1 retrotransposons. Clinical Cancer Research, 2024, pp.OF1-OF17. ⟨10.1158/1078-0432.ccr-24-2669⟩. ⟨hal-04830936⟩

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