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Updated: Jan 14, 2026
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Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
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Evaluation of reference sample type for somatic variant calling in myeloid cancers
Maja Z Jakobsen1,2,3, Emil-August Torp4, Issa I Issa1,2,5,6,3
1Department of Hematology, Aalborg University Hospital, Søndre Skovvej 15, Aalborg, 9000, Denmark.
Annals of Hematology
|October 22, 2025
Summary
For myeloid cancers, T-cells are the best normal reference for whole exome sequencing (WES) to accurately identify somatic variants. Tumor-only analysis is a viable alternative with careful filtration.
Area of Science:
- Genomics
- Oncology
Background:
- Accurate somatic variant identification in cancer requires comparing tumor and normal DNA.
- High-throughput sequencing, including whole exome sequencing (WES), is crucial for cancer diagnostics and personalized medicine.
Purpose of the Study:
- To determine the optimal normal reference sample for WES in myeloid-derived cancers.
- To evaluate T-cells, skin biopsies, and saliva as reference samples compared to tumor-only analysis.
Main Methods:
- Compared variant calls from tumor-reference pairs against tumor-fibroblast analyses.
- Assessed sensitivity and false positive rates for different normal reference samples and tumor-only analysis.
Main Results:
- T-cells showed the highest sensitivity (0.91-1.00) and lowest false positive rate.
- Skin biopsies and saliva provided inconsistent results due to potential contamination.
- Tumor-only analysis had high sensitivity but generated false positives, manageable with filtration.
Conclusions:
- T-cells represent the optimal reference sample for accuracy and practicality in myeloid cancer WES.
- Tumor-only analysis with selective filtration is a feasible alternative for somatic variant detection.
- Optimized workflows enhance genomic profiling for personalized cancer treatment.
