The Effect of Unique Molecular Identifier Family Size Using Tumor-Informed Circulating Tumor DNA Analysis in Childhood Cancers
Journal article, 2026
Analysis of circulating tumor DNA (ctDNA) provides a molecular assessment that can complement routine imaging in childhood cancer management. Detailed monitoring of ctDNA levels may provide information on treatment efficacy and resistance and minimal residual disease and allows for early detection of relapse. Here, tumor-informed ctDNA analysis was applied to 90 blood plasma samples collected from eight children with malignant tumors. A total of 4 to 10 tumor-specific mutations per patient were assessed using SiMSen-Seq, a digital sequencing approach using unique molecular identifiers (UMIs). The effects of individual SiMSen-Seq assays and plasma samples were evaluated in relation to their impact on background error rate, number of detected target molecules, and mutant calling using different UMI family size cutoff settings. The use of at least two sequencing reads per UMI provided the best overall performance by generating the highest number of detected target molecules and hence the optimal chance to detect low-frequency mutations. Data were consistent between SiMSen-Seq assays and plasma samples, providing robust ctDNA profiling over time for all patients. In conclusion, the results show that optimal use of UMIs in tumor-informed ctDNA analysis enables sensitive molecular readout that can assist in management of childhood cancers.
ctDNA
cancer
childhood cancers
imaging
Author
Tobias Österlund
University of Gothenburg
Sahlgrenska University Hospital
Daniel Andersson
University of Gothenburg
Raghda R. Ibrahim
University of Gothenburg
Elisabeth Mellström
Sahlgrenska University Hospital
University of Gothenburg
Jenny Lundmark
RISE Research Institutes of Sweden
Junrui Li
University of Gothenburg
Stefan Filges
University of Gothenburg
Simsen Diagnostics AB
Peter Micallef
Sahlgrenska University Hospital
University of Gothenburg
Manuel Luna Santamaría
University of Gothenburg
Mandy Escobar
University of Gothenburg
Pia Mouhanna
County Hospital Ryhov
University of Gothenburg
Firaol T. Kebede
University of Gothenburg
Christoffer Vannas
University of Gothenburg
Sahlgrenska University Hospital
Ida Rahmqvist
University of Gothenburg
Fani Pujol-Calderón
University of Gothenburg
Agnes Dahlstrand Rudin
University of Gothenburg
Wilma Franssila
University of Gothenburg
Åsa Torinsson Naluai
University of Gothenburg
Sahlgrenska University Hospital
Serik Sagitov
Chalmers, Mathematical Sciences
Joakim Håkansson
RISE Research Institutes of Sweden
University of Gothenburg
Henrik Fagman
Sahlgrenska University Hospital
University of Gothenburg
Martin Dalin
University of Gothenburg
Sahlgrenska University Hospital
Anders Ståhlberg
University of Gothenburg
Sahlgrenska University Hospital
Journal of Molecular Diagnostics
1525-1578 (ISSN) 19437811 (eISSN)
Vol. In PressSubject Categories (SSIF 2025)
Cancer and Oncology
DOI
10.1016/j.jmoldx.2026.08.002
PubMed
42727690
Related datasets
Supplemental data [dataset]
DOI: 10.1016/j.jmoldx.2026.08.002