Multi-site pre-therapeutic biopsies demonstrate genetic heterogeneity in patients with newly diagnosed diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, both regarding clinical presentation, response to treatment and outcome. Recently, subclassification of DLBCL based on mutational profile has been suggested, and next generation sequencing (NGS) analysis may be relevant as part of the diagnostic workflow. This will, however, often be based on analysis of one tumor biopsy. Here, we present a prospective study where multi-site sampling was performed prior to treatment in patients with newly diagnosed DLBCL. Two spatially different biopsies from 16 patients were analyzed using NGS with an in-house 59-gene lymphoma panel. In 8/16 (50%) patients, mutational differences were found between the two biopsy sites, including differences in TP53 mutational status. Our data indicate that a biopsy from the extra-nodal site may represent the most advanced clone, and an extra-nodal biopsy should be preferred for analysis, if safely accessible. This will help ensure a standardized stratification and treatment decision.

Keywords:

• Genetic heterogeneity
• TP53
• lymphoma
• diffuse large B-cell
• extra-nodal

Acknowledgments

We thank all the patients for their participating in the project. A special thanks to Biomedical laboratory Scientist Christina Grønhøj for all her work and technical support.

Author contributions

Ditte Stampe Hersby: performed the research, analyzed the data, and wrote the paper. Lone Schejbel: performed the next generation sequencing analysis, analyzed the data, and wrote the paper. Marie Breinholt: performed all pathological assessments in the project. Writing—review and editing. Estrid Høgdall: writing—review and editing. Peter Nørgaard: writing—review and editing. Ditte Dencker: performed all assessments of scans—performed all biopsies in the project. Writing—review and editing. Torsten Holm Nielsen: supervision. Writing—review and editing. Lars Møller Pedersen: supervision. Writing—review and editing. Anne Ortved Gang: designed the study, supervision, writing—review and editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The former Hematology department at Herlev Hospital funded the next generation sequencing analyses.