Dataset for the manuscript Identifying somatic mutations in aggressive non-Hodgkin B-cell lymphoma with enhanced specificity using liquid biopsy: A comparative study of circulating tumor DNA and FFPE tissue

ABSTRACT Background: Circulating tumor DNA (ctDNA) has the potential to overcome key obstacles posed by formalin-fixed paraffin-embedded (FFPE) tissue. We aimed to evaluate the genomic concordance and performance of ctDNA and FFPE tissue using a custom 53-gene panel with unique molecular identifiers. Methods: Fifteen patients with aggressive non-Hodgkin B-cell lymphoma were included. Paired diagnostic FFPE tissue and cfDNA from pre-treatment plasma were sequenced for all patients alongside matched peripheral blood mononuclear cells for eight of the patients. Results: A total of 102 somatic variants were identified and shared between ctDNA and FFPE DNA. ctDNA and FFPE had a median of 6 (1; 12) and 49 (11; 190) variants, respectively. ctDNA markers were found in 12/15 patients. A variant allele frequency (VAF) threshold of 1% and 10% was applied for ctDNA and FFPE DNA, respectively. The performance of the ctDNA assay was evaluated using precision-recall analysis, which demonstrated a maximum precision of 83% at an FFPE VAF > 50%. Using COSMIC as a surrogate truth set, the fraction of variants reported in COSMIC was twice as high in cfDNA (0.22) compared to the FFPE (0.11) at a 10% VAF. Conclusion: This single-center study demonstrates the feasibility of ctDNA as an analyte using a custom gene panel with UMIs in patients with aggressive non-Hodgkin B-cell lymphoma. cfDNA provides superior specificity compared to FFPE tissue DNA for the detection of somatic variants at a VAF of 1%, while the sensitivity of FFPE is higher.