Circulating tumor DNA in primary mediastinal large B-cell lymphoma versus classical Hodgkin lymphoma: a retrospective study

Abstract

Few data exist concerning circulating tumor DNA (ctDNA) relevance in primary mediastinal B-cell lymphoma (PMBL). To explore this topic, we applied a 9-gene next-generation sequencing pipeline to samples from forty-four PMBL patients (median age 36.5 years). The primary endpoint was a similarity between paired biopsy/plasma mutational profiles. We detected at least one variant in 32 plasma samples (80%). The similarity between the biopsy and ctDNA genetic profiles for the 30 patients with paired mutated biopsy/plasma samples was greater than or equal to 80% in 19 patients (63.3%). We then compared PMBL ctDNA features with those of a cohort of Hodgkin lymphoma patients (n = 60). The top three mutated genes were SOCS1, TNFAIP3, and B2M in both lymphoma types. PMBL displayed more alterations in TNFAIP3 (71.9% vs. 46.3%, p = 0.029) and GNA13 (46.9% vs. 17.1%, p = 0.013) than cHL. Our 9-gene set may delineate tumor genotypes using ctDNA samples from both lymphoma types.

Keywords:

• Primary mediastinal large B cell lymphoma
• classical Hodgkin lymphoma
• circulating tumor DNA
• cell-free DNA

Acknowledgments

The authors thank the patients and their families. The authors thank Dr Jean-Michel Picquenot for support in pathological review. The authors thank Mrs. Doriane Richard, CRA manager, for administrative support in this study. The authors wish to thank the Biological Resource Center (CRB – Rouen) and the Department of Oncology Genetics of the Henri Becquerel Center for the processing of the samples.

Author contributions

VC designed and supervised the study, analyzed and interpreted the data and wrote the manuscript. VC, FJ, HT, and SD took care of the patients, collected clinical data and edited the paper. MV and EB performed Next-Generation Sequencing experiments. DT performed PET-scans review and MTV measurements. FD and ELV performed pathological review. PJV performed the bioinformatics analysis. EL performed the statistical analysis. FJ designed and supervised the study, analyzed and interpreted the data, and edited the paper. All authors approved the manuscript.

Disclosure statement

The authors declare no conflicts of interest relevant to this study. Relevant financial activities outside the submitted work: VC: Honoraria: Roche, Amgen; Gilead-Kite, BMS, Sanofi; Travel Grants: Pfizer, Roche. HT: Honoraria: Celgene, Roche, Karyopharm, Astra-Zeneca, Bristol-Myers Squibb, Grants: Celgene.

Additional information

Funding

This work was supported by grants from the Center Henri Becquerel under grant [CHB-INT-2017] and the Ligue Contre le Cancer (Comité de l’Eure) under grant [AO-2017].