Circulating tumor DNA assisting lymphoma genetic feature profiling and identification

Area of Science:

• Oncology
• Genetics
• Molecular Diagnostics

Background:

• Lymphoma tissue biopsies present challenges in capturing comprehensive genetic features due to accessibility and tumor heterogeneity.
• Circulating tumor DNA (ctDNA) presents a promising non-invasive alternative for genomic analysis.

Purpose of the Study:

• To assess the utility of ctDNA for genomic profiling in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL).
• To evaluate ctDNA for disease surveillance and monitoring treatment response in these lymphoma subtypes.

Main Methods:

• Next-generation sequencing of 475 genes was performed on tumor tissue and/or liquid biopsies from 49 cHL, 32 PMBCL, and 74 DLBCL patients.
• Concordance analysis between ctDNA and tissue-based genetic aberrations was conducted.
• ctDNA mutational landscapes were analyzed, and ctDNA dynamics were correlated with treatment response and radiological progression.

Main Results:

• ctDNA demonstrated high concordance with tissue samples across cHL (78%), PMBCL (84%), and DLBCL (78%).
• ctDNA detected unique mutations and higher variant allele frequencies in cHL compared to tissue biopsies.
• Distinct genomic alterations, including STAT6, SOCS1, BTG2, and PIM1, were identifiable via ctDNA.
• ctDNA dynamics correlated with treatment response and could predict relapse before imaging.

Conclusions:

• Genomic profiling of lymphomas using ctDNA is highly concordant with traditional tissue biopsy methods.
• ctDNA is a valuable tool for lymphoma surveillance and holds potential for guiding treatment decisions.