Assessment of Liquid Biopsy in Primary Cutaneous Diffuse Large B-Cell Lymphoma–Leg Type

Abstract

Liquid biopsy assessment has been first established in solid tumors, allowing the detection of either circulating tumor cells, cell-free vesicles and/or circulating tumor cell-free DNA (ctDNA), in the plasma or other biological fluids. In systemic diffuse large B-cell lymphomas (DLBCL), ctDNA is detectable, reflecting tumor mutational status, and may predict clinical outcome ( Bohers et al., 2018 Bohers E, Viailly P-J, Becker S, Marchand V, Ruminy P, Maingonnat C, et al. Non-Invasive Monitoring of Diffuse Large B-Cell Lymphoma by Cell-Free DNA High-Throughput Targeted Sequencing: Analysis of a Prospective Cohort. Blood Cancer J. 2018;1;8(8):74. Google Scholar ). In addition, dynamics of ctDNA correlates with clinical response ( Kurtz et al., 2019 Kurtz D.M. Esfahani M.S. Scherer F. Soo J. Jin M.C. Liu C.L. et al. Dynamic risk profiling using serial tumor biomarkers for personalized outcome Prediction. Cell. 2019; 178: 699-713.e19 Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar ; Deng et al., 2020 Deng Q, G Han, N Puebla-Osorio, M Chun John Ma, P Strati, B Chasen, et al. Characteristics of Anti-CD19 CAR T Cell Infusion Products Associated with Efficacy and Toxicity in Patients with Large B Cell Lymphomas. Nat Med. 2020;26 (12): 1878-1887. Google Scholar ; Kurtz et al. 2018). Primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT) is an aggressive cutaneous lymphoma, presenting as rapid progressive tumor(s) in elderly ( Willemze et al., 2019 Willemze R. Cerroni L. Kempf W. Berti E. Facchetti F. Swerdlow S.H. Jaffe E.S. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019; 133: 1703-1714 Crossref PubMed Scopus (535) Google Scholar ). Mutational landscape of PCDLBCL-LT showed Activated B-cell-like DLBCL canonical mutations, ( Mareschal et al., 2017 Mareschal S. Pham-Ledard A. Viailly P.J. Dubois S. Bertrand P. Maingonnat C. et al. Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing. J Invest Dermatol. 2017; 137: 1984-1994 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar ; Zhou et al. 2018) especially with high prevalence of MYD88L265P (70%) and CD79B (40%) mutations that allows its classification in MCD or C5 subgroup among DLBCL ( Schmitz et al., 2018 Schmitz R. Wright G.W. Huang D.W. Johnson C.A. Phelan J.D. Wang J.Q. et al. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Eng J Med. 2018; 378: 1396-1407 Crossref PubMed Scopus (936) Google Scholar ) ( Chapuy et al., 2018 Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. 2018. Molecular Subtypes of Diffuse Large B-cell Lymphoma are Associated with Distinct Pathogenic Mechanisms and Outcomes ». Nat Med. 2018;24(5):679-690. Google Scholar ). Genetic analysis on primary tumors may be limited by tumor site, sample size but also by spatial and temporal mutational heterogeneity (Condoluci et Rossi 2019; Phallen et al., 2017 Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, et alDirect detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017;16;9(403):eaan2415. Google Scholar ). Droplet digital PCR (ddPCR) and its increased sensitivity of 0.01% (Diaz et Bardelli 2014) may detect infraclinical systemic involvement and appears appropriate for single hot-spot mutations detection such as MYD88L265P. Next Generation Sequencing (NGS) may be more appropriate to capture the mutational landscape of ctDNA ( Galimberti et al., 2019 Galimberti S. Genuardi E. Mazziotta F. Iovino L. Morabito F. Grassi S. et al. The Minimal Residual Disease in Non-Hodgkin’s Lymphomas: From the Laboratory to the Clinical Practice. Front Oncol. 2019; 26: 528 Crossref Scopus (14) Google Scholar ).