Liquid Biopsy for Enhanced Specificity in Identifying Somatic Mutations in Aggressive Non-Hodgkin Large B-Cell Lymphoma: A Comparative Study of Cell-Free DNA and Formalin-Fixed Paraffin-Embedded Tissue

被引：0

作者：

Vimalathas, Gayaththri ^{[1
,2
,3
,4
,5
]}

Cedile, Oriane ^{[2
,3
,4
,6
,7
,8
]}

Kjeldsen, Marie Louise Grube ^{[2
,3
,4
,6
]}

Thomassen, Mads ^{[1
,9
,10
]}

Moller, Michael Boe ^{[1
,2
,3
,4
,5
]}

Nyvold, Charlotte Guldborg ^{[1
,2
,3
,4
,6
,7
,8
]}

Hansen, Marcus Hoy ^{[1
,2
,3
,4
,6
,7
]}

Larsen, Thomas Stauffer ^{[1
,2
,3
,4
,6
,7
]}

机构：

[1] Univ Southern Denmark, Dept Clin Res, Odense, Denmark

[2] Univ Southern Denmark, Res Unit Haematol, Haematol Pathol Res Lab, Odense, Denmark

[3] Univ Southern Denmark, Res Unit Pathol, Odense, Denmark

[4] Odense Univ Hosp, Odense, Denmark

[5] Odense Univ Hosp, Dept Pathol, Odense, Denmark

[6] Odense Univ Hosp, Dept Haematol, Odense, Denmark

[7] Odense Univ Hosp, Ctr Cellular Immunotherapy Haematol Canc Odense, CITCO, Odense, Denmark

[8] Odense Univ Hosp, OPEN, Odense Patient Data Explorat Network, Odense, Denmark

[9] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark

[10] Univ Southern Denmark, Clin Genome Ctr, Dept Clin Res, Odense, Denmark

来源：

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY | 2025年

关键词：

B-cell lymphoma; cell-free DNA; circulating tumor DNA; DNA sequence analysis; CIRCULATING TUMOR DNA; DROSOPHILA-MELANOGASTER; BREAKPOINTS; PROGRAM; GENOME;

D O I：

10.1111/ijlh.14454

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction: Formalin-fixed paraffin-embedded (FFPE) tumor biopsy is the current mainstay of genotyping, but is limited by its invasiveness and tumor heterogeneity. Plasma cell-free DNA (cfDNA) constitutes a minimally invasive alternative that may better capture tumor-derived profiles from circulating tumor DNA (ctDNA). This study compares the performance and genomic concordance of cfDNA and FFPE tumor DNA in aggressive non-Hodgkin large B-cell lymphoma. Methods: Paired diagnostic FFPE tissue and plasma samples from 15 patients were sequenced with a custom 53-gene panel. Results: Detection thresholds were empirically guided at 1% variant allele frequency (VAF) for cfDNA and 10% for unpaired FFPE DNA. The median number of cfDNA variants was 6 (interquartile range (IQR): 2-11) versus 63 (IQR: 15-250) in FFPE DNA at 1% VAF. Collectively, 102 somatic variants were shared between cfDNA and FFPE DNA with a median of 5 (range: 0-23). cfDNA showed a five-fold lower median VAF for shared variants than FFPE DNA (7% vs. 36%, p < 0.0001). Eighty percent of patients harbored at least one cfDNA variant. A maximum cfDNA recall rate of 83% was observed at FFPE DNA VAF > 50%. COSMIC database overlap was twice as high for cfDNA compared to FFPE DNA (22% vs. 11%) at 10% VAF. Conclusionc: fDNA has superior specificity for somatic mutation detection but lower sensitivity than FFPE DNA. Modest concordance was demonstrated between the two compartments. Our results support a complementary role of ctDNA in mutational profiling at a 1% VAF threshold in a pragmatic and clinically applicable setup.

引用

页数：11