Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
by
, , , ,
Gloria Figaredo
1,*
,
Alejandro Martín-Muñoz
2,
Santiago Barrio
2,3,
Laura Parrilla
1,
Yolanda Campos-Martín
4,
María Poza
5,
Laura Rufián
2,5,
Patrocinio Algara
6,
Marina De La Torre
1,
Ana Jiménez Ubieto
5,
Joaquín Martínez-López
5
,
Luis-Felipe Casado
1,† and
Manuela Mollejo
7,† 1
Department of Haematology, Hospital Universitario de Toledo, Av. del Río Guadiana, 45007 Toledo, Spain
2
Altum Sequencing SL, Av. Gregorio Peces Barba, 1, 28919 Madrid, Spain
3
Computational Science Department, Carlos III University, Ronda de Toledo, 1, 28005 Madrid, Spain
4
Biobank Department, Hospital Universitario de Toledo, Av. del Río Guadiana, 45007 Toledo, Spain
5
Haematology Department, Hospital Universitario 12 de Octubre, Avda. de Córdoba, s/n, 28041 Madrid, Spain
6
Genetics Department, Hospital Universitario de Toledo, Av. del Río Guadiana, 45007 Toledo, Spain
7
Anatomopathology Department, Hospital Universitario de Toledo, Av. del Río Guadiana, 45007 Toledo, Spain
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2023, 15(16), 4022; https://doi.org/10.3390/cancers15164022
Submission received: 7 July 2023
/
Revised: 26 July 2023
/
Accepted: 6 August 2023
/
Published: 8 August 2023
(This article belongs to the Special Issue Measurable Residual Disease in Cancer)
Simple Summary
Genetic profiling of plasma cell-free DNA (cfDNA) from liquid biopsies (LiqBio) is a possible alternative to genetic profiling of tissue biopsies to diagnose B-cell lymphoma (BCL), and a complementary tool of PET/CT to determine measurable residual disease (MRD). The aim of our study was to confirm the utility of LiqBio for diagnosis and surveillance of BCL. We confirmed the correlation between somatic mutations in paired LiqBio and tissue biopsies at diagnosis in a population of 78 patients; furthermore, we identified additional mutations in LiqBio at diagnosis from patients with no available tissue samples or no mutations detected in tissue samples. As a surveillance tool for MRD detection, LiqBio combined with PET/CT showed to be a valuable method, improving the PET/CT specificity.
Abstract
Purpose: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. Methods: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio–MRD method with PET/CT in detecting MRD at follow-up. Results: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio–MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio–MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). Conclusion: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance.
Keywords:
B-cell lymphoma; liquid biopsies; cfDNA; NGS; minimal residual disease; PET/CT
