Genotyping on ctDNA Identifies Shifts in Mutation Spectrum Between Newly Diagnosed and Relapse/Refractory DLBCL

Abstract

Hui Liu,1,2,* Chunmei Yang,2,3,* Xiaoyan Zhao,2,4 Jing Le,5 Gongqiang Wu,6 Juying Wei,2,3 Yun Liang,1 Wenbin Qian1,2 1Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, People’s Republic of China; 2Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 31003, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People’s Republic of China; 4Department of Hematology, First Affiliated Hospital of Jiaxing University, Jianxing, Zhejiang 314000, People’s Republic of China; 5Department of Hematology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, People’s Republic of China; 6Department of Hematology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang People’s Hospital, Dongyang, Zhejiang 322100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenbin Qian; Yun LiangDepartment of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of ChinaTel [phone]Email [email protected]; [email protected]: Diffuse large B cell lymphoma (DLBCL) is an aggressive B-cell malignancy with clinical and molecular heterogeneity whose genetics may have clinical implications for patient stratification and treatment. The circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker harboring tumor-derived genetic alterations that are identical to those of tumor cells, thus showing great promise in individualized medicine, including precise diagnosis, prediction of prognosis, response monitoring, and relapse detection for DLBCL.Patients and Methods: In this study, we applied NGS analysis to tumor biopsies and ctDNA samples from 16 DLBCL subjects. Then, we compared the genomic alterations from 41 newly diagnosed patients and 56 relapsed/refractory (R/R) patients.Results: Our results show that ctDNA can function as a liquid biopsy for tracking recurrently mutated genes in DLBCL (sensitivity: 87.50%). The mutational profiles of newly diagnosed and R/R DLBCL groups largely overlapped, but the frequencies of some gene mutations differ between the two cohorts. The distribution of mutations also revealed different frequencies in the two cohorts due to different signaling pathways. Genes from apoptosis pathway, immune response and BCR pathway suffered more mutations in R/R patients.Conclusion: Overall, this study establishes ctDNA as an easily accessible source of tumor DNA for DLBCL genotyping and provides a deeper understanding of the somatic alteration spectrum for both newly diagnosed and R/R DLBCL patients.Keywords: diffuse large B cell lymphoma, circulating tumor DNA, liquid biopsy, next-generation sequencing, mutation

Keywords

• diffuse large b cell lymphoma
• circulating tumor dna
• liquid biopsy
• next-generation sequencing
• mutation