Circulating tumor DNA assisting lymphoma genetic feature profiling and identification

• Published in: Annals of hematology Vol. 103; no. 10; pp. 4135 - 4144
• Main Authors: Wang, Hongbiao, Wang, Zhao, Zhu, Sujuan, Li, Zhifeng, Yang, Hang, Sun, Peng, Zhu, Minyi, Zhao, Xiaotian, Shen, Lu, Ou, Qiuxiang, Yang, Hui, Li, Zhi-Ming
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2024; Springer Nature B.V
• Subjects: Adult; Aged; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biopsy; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Female; Hematology; High-Throughput Nucleotide Sequencing; Hodgkin Disease - blood; Hodgkin Disease - diagnosis; Hodgkin Disease - genetics; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse - blood; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Mediastinal Neoplasms - genetics; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Disease surveillance; Lymphoma; Primary mediastinal large B-cell lymphoma; Circulating tumor DNA; Classic Hodgkin lymphoma; Diffuse large B-cell lymphoma
• ISSN: 0939-5555; 1432-0584; 1432-0584
• DOI: 10.1007/s00277-024-05782-0

Introduction Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). Methods Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. Results ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies ( P  < 0.01), with higher variant allele frequencies ( P  < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6 , SOCS1 , BTG2 , and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL ( P  < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. Conclusions Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.