Evaluation of reference sample type for somatic variant calling in myeloid cancers.

ABSTRACT: High-throughput sequencing is transforming cancer diagnostics, research, and clinical decision-making, yet accurate identification of disease-driving somatic variants often requires comparing tumor and normal DNA. This study aimed to identify the optimal normal reference sample for whole exome sequencing (WES) in myeloid-derived cancers. T-cells, skin biopsies, saliva, and a tumor-only analysis were evaluated by comparing variant calls from tumor-reference pair to those from tumor-fibroblast analyses. T-cells demonstrated the highest sensitivity (0.91-1.00) and lowest false positive rate, establishing them as a reliable reference option. Skin biopsies and saliva yielded inconsistent results, likely due to leucocytic contamination. While tumor-only analysis offered high sensitivity, it gene

SUBMITTER: Jakobsen MZ 

PROVIDER: S-EPMC12672828 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature