Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential.

Abstract

Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed. At diagnosis, liquid biopsies showed detectable copy number alterations in 84.2% of HL (88.6% for classical HL) and 74.1% of DLBCL patients. Copy number profiles between liquid-solid pairs were highly concordant within DLBCL (r=0.815±0.043); and, compared to tissue, HL liquid biopsies had abnormalities with higher amplitudes (P=.010), implying that tumor DNA is more abundant in plasma. Additionally, 39.5% of HL and 13.6% of DLBCL cases had a significantly elevated number of plasmatic Epstein-Barr virus DNA fragments, achieving a sensitivity of 100% compared to current standard. Longitudinal analysis determined that, when detectable, copy number patterns were similar across (re)staging moments in refractory/relapsed patients. Moreover, the overall profile anomaly highly correlated with the total metabolic tumor volume (P.

• Authors: Lennart Raman, Malaïka Van der Linden, Ciel De Vriendt, Bliede Van den Broeck, Kristoff Muylle, Dries Deeren, Franceska Dedeurwaerdere, Sofie Verbeke, Amélie Dendooven, Katrien De Grove, Saskia Baert, Kathleen Claes, Björn Menten, Fritz Offner, Jo Van Dorpe
• Journal: Haematologica (Haematologica) Vol. 107 Issue 1 Pg. 211-220 (01 01 2022) ISSN: 1592-8721 [Electronic] Italy
• PMID: 33299235 (Publication Type: Journal Article)

Chemical References

• Cell-Free Nucleic Acids

Topics

• Cell-Free Nucleic Acids
• Epstein-Barr Virus Infections
• Herpesvirus 4, Human (genetics)
• Hodgkin Disease (diagnosis, genetics)
• Humans
• Lymphoma, Large B-Cell, Diffuse (diagnosis, genetics)