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Diffuse large B-cell lymphoma genotyping on the liquid biopsy.

Davide Rossi^1,2, Fary Diop¹, Elisa Spaccarotella¹

¹Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.

|January 19, 2017

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Plasma cell-free DNA (cfDNA) genotyping accurately detects diffuse large B-cell lymphoma (DLBCL) mutations and non-invasively tracks treatment resistance and clonal evolution in real-time.

Area of Science:

Oncology
Genetics
Molecular Biology

Background:

Diffuse large B-cell lymphoma (DLBCL) requires accessible and real-time genetic profiling for diagnosis, prognosis, and treatment.
Tumor-derived cell-free DNA (cfDNA) in plasma offers a non-invasive source for identifying DLBCL mutations and tracking clonal dynamics.

Purpose of the Study:

To assess the accuracy of plasma cfDNA genotyping for detecting DLBCL mutations.
To evaluate cfDNA's utility in monitoring treatment response and identifying resistance mechanisms in DLBCL patients.

Main Methods:

Ultra-deep targeted next-generation sequencing of plasma cfDNA from DLBCL patients.
Comparison of cfDNA genotyping results with tumor biopsy data.
Longitudinal plasma cfDNA analysis during rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) chemotherapy.

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Main Results:

Plasma cfDNA genotyping demonstrated high sensitivity and specificity for detecting DLBCL mutations present in tumor biopsies.
cfDNA analysis identified mutations missed by tissue biopsy, potentially due to tumor heterogeneity.
Responders to R-CHOP showed rapid clearance of DLBCL mutations in cfDNA, while non-responders exhibited persistent and newly acquired mutations indicating resistance.

Conclusions:

Plasma cfDNA genotyping is a reliable and accurate alternative to tumor biopsy for DLBCL mutation detection.
cfDNA analysis provides a real-time, non-invasive method for tracking DLBCL clonal evolution and the emergence of treatment resistance during therapy.