Circulating tumor DNA mutation profile is associated with the prognosis and treatment response of Chinese patients with newly diagnosed diffuse large B-cell lymphoma

Tao Guan; Min Zhang; Xiaolan Liu; Jing Li; Beibei Xin; Yanxin Ren; Yuchao Yang; Hui Wang; Mengjing Zhao; Yunpeng Huang; Xiaojing Guo; Jun Du; Wenbin Qian; Liping Su

doi:10.3389/fonc.2022.1003957

Circulating tumor DNA mutation profile is associated with the prognosis and treatment response of Chinese patients with newly diagnosed diffuse large B-cell lymphoma

Front Oncol. 2022 Nov 17:12:1003957. doi: 10.3389/fonc.2022.1003957. eCollection 2022.

Authors

Tao Guan¹, Min Zhang¹, Xiaolan Liu¹, Jing Li², Beibei Xin³, Yanxin Ren⁴, Yuchao Yang¹, Hui Wang¹, Mengjing Zhao⁵, Yunpeng Huang¹, Xiaojing Guo¹, Jun Du⁶, Wenbin Qian⁷, Liping Su¹

Affiliations

¹ Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
² Department of Pathology, Shanxi Cancer Hospital, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, China.
³ Department of Medicine, Shanghai Yuanqi Biomedical Technology Co., Ltd., Shanghai, China.
⁴ Department of Technology, Shanghai Yuanqi Biomedical Technology Co., Ltd., Shanghai, China.
⁵ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.
⁶ Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
⁷ Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Abstract

Background: Characterization of gene mutation profiles can provide new treatment options for patients with diffuse large B-cell lymphoma (DLBCL). However, this method is challenged by the limited source of tissue specimens, especially those of DLBCL patients at advanced stages. Therefore, in the current study, we aimed to describe the gene mutation landscape of DLBCL using circulating tumor DNA (ctDNA) samples obtained from patients' blood samples, as well as to explore the relationship between ctDNA mutations and the prognosis and treatment response of patients with newly diagnosed DLBCL.

Methods: A total of 169 newly diagnosed Chinese DLBCL patients were included in this study, among which 85 patients were divided into a training set and 84 were assigned into a validation set. The mutation profile of a 59-gene panel was analyzed by targeted next generation sequencing (NGS) of the patients' ctDNA samples. Differences in clinical factors between patients with and without ctDNA mutations were analyzed. In addition, we also explored gene mutation frequencies between GCB and non-GCB subtypes, and the relationship between gene mutation status, clinical factors, mean VAF (variant allele frequencies) and the patients' overall survival (OS) and progression-free survival (PFS).

Results: ctDNA mutations were detected in 64 (75.3%) patients of the training set and 67 (79.8%) patients of the validation set. The most commonly mutated genes in both sets were PCLO, PIM1, MYD88, TP53, KMT2D, CD79B, HIST1H1E and LRP1B, with mutation frequencies of >10%. Patients with detectable ctDNA mutations trended to present advanced Ann Arbor stages (III-IV), elevated LDH (lactate dehydrogenase) levels, shorter OS and PFS, and a lower complete response (CR) rate to the R-CHOP regimen compared with DLBCL patients without ctDNA mutations. In addition, mean VAF (≥4.94%) and PCLO mutations were associated with poor OS and PFS.

Conclusion: We investigated the ctDNA mutation landscape in Chinese patients with newly diagnosed DLBCL and found that ctDNA could reflect tumor burden and patients with detectable ctDNA mutations trended to have shorter OS and PFS and a lower CR rate.

Keywords: circulating tumor DNA; diffuse large B cell lymphoma; mutation; prognosis; targeted next-generation sequencing.