Related Experiment Video
Updated: Jun 6, 2025
Detection of Retrotransposition Activity of Hot LINE-1s by Long-Distance Inverse PCR
Published on: July 27, 2019
Noninvasive Multicancer Detection Using DNA Hypomethylation of LINE-1 Retrotransposons
Marc Michel1,2,3,4, Maryam Heidary4, Anissa Mechri1,5
1Inserm U934, CNRS UMR3215, Institut Curie, PSL Research University, Paris, France.
Purpose:
The detection of ctDNA, which allows noninvasive 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 bp resolution methylation patterns from plasma DNA and assessed the potential of hypomethylation of long interspersed nuclear element-1 retrotransposons as a noninvasive multicancer detection biomarker. The Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA method targets 30 to 40,000 young long interspersed nuclear element-1 retrotransposons 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 six types of cancers (colorectal, breast, lung, ovarian, and gastric cancers and uveal melanoma, including localized stages) in two independent cohorts (AUC = 88%-100%, N = 747). The Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA method can also be used to perform copy number alteration analysis that improves cancer detection.
Conclusions:
This should lead to the development of more efficient noninvasive diagnostic tests adapted to all patients with cancer, based on the universality of these factors. See related commentary by Szymanski et al., p. 1179.
Insights
A new method detects cancer DNA in blood by analyzing methylation patterns of long interspersed nuclear element-1 retrotransposons. This noninvasive approach shows high accuracy for detecting multiple cancer types, including early stages.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Circulating tumor DNA (ctDNA) enables noninvasive cancer profiling and monitoring.
- Detecting low levels of ctDNA, especially during reduced tumor burden, remains a significant challenge.
Purpose of the Study:
- To develop a highly sensitive strategy for detecting methylation patterns in plasma DNA.
- To evaluate hypomethylation of long interspersed nuclear element-1 (LINE-1) retrotransposons as a multicancer biomarker.
Main Methods:
- Implemented a novel method targeting 30-40,000 LINE-1 retrotransposons across ~100,000 CpG sites.
- Utilized a reference-free analysis pipeline and machine learning classifiers.
- Assessed copy number alterations for enhanced cancer detection.
Main Results:
- Achieved high classification rates distinguishing healthy and tumor plasmas across six cancer types (colorectal, breast, lung, ovarian, gastric, uveal melanoma).
- Demonstrated effectiveness in two independent cohorts with AUC values ranging from 88% to 100% (N = 747).
- Included detection of localized cancer stages.
Conclusions:
- The developed method shows potential for efficient, noninvasive diagnostic tests for cancer patients.
- The universality of LINE-1 hypomethylation suggests broad applicability across various cancer types.
- This approach could significantly advance individualized cancer management.
