Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma - PubMed

4 days ago

Liquid biopsies and cell-free DNA (cfDNA) provide minimally invasive methods for diagnosing and monitoring Ewing Sarcoma (EwS).
EwS has a low tumor mutational burden, making detection via plasma cfDNA challenging.
Analysis of cfDNA methylome and fragmentome enhances sensitivity for detecting EwS and identifying disease recurrence.
T7-MBD-seq was used for whole-genome and methylome sequencing of cfDNA from 87 samples of 23 EwS patients and 3 CIC-rearranged sarcoma patients.
EwingSign, a machine learning model, detected EwS or CIC in 11 out of 16 patients at diagnosis and 15 out of 18 relapse events.
No false positives were found in 24 non-cancer controls (NCC) using EwingSign.
Combining methylome and fragmentome analysis detected all 18 relapse cases, with 15/18 detected by 2 or more methods.
One false positive was observed in 24 NCC when using combined modalities.
The findings suggest cfDNA methylome and fragmentome analysis could improve EwS detection, monitoring, and relapse identification if validated in larger cohorts.

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