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. 2022 Jul 5:12:901547.
doi: 10.3389/fonc.2022.901547. eCollection 2022.

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

Xiao-Bo Wu  1   2 , Shu-Ling Hou  1   2 , Qiao-Hua Zhang  1   2 , Ning Jia  3 , Min Hou  2   4 , Wen Shui  5
Affiliations

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

Xiao-Bo Wu et al. Front Oncol. .

Abstract

Background: Lymphoma is a heterogeneous group of tumors in terms of morphological subtypes, molecular alterations, and management. However, data on circulating tumor DNA (ctDNA) mutated genes are limited. The purpose of this study was to investigate the features of the ctDNA mutated genes, the prognosis, and the association between the ctDNA mutated genes and the clinical parameters in lymphoma.

Methods: Differences in the ctDNA between the mutated genes and the prognosis of 59 patients with Hodgkin's lymphoma (HL) (10.2%), germinal center B-cell-like lymphoma (GCB) (28.8%), nongerminal center B-cell-like lymphoma (non-GCB) (50.8%), and marginal zone lymphoma (MZL) (10.2%) were analyzed by next generation sequencing (NGS) targeting 121 lymphoma-relevant genes.

Results: Genetic alterations were identified in the ctDNA samples with a median of 6 variants per sample. The genetic variation of the ctDNA in the plasma was found to be significantly correlated with the clinical indices in lymphoma. The genetic heterogeneity of different lymphoma subtypes was clearly observed in the ctDNAs from HL, GCB, non-GCB, and MZL, confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas.

Conclusion: Our findings suggest that NGS-based ctDNA mutation analysis reveals genetic heterogeneity across lymphoma subtypes, with potential implications for discovering therapeutic targets, exploring genomic evolution, and developing risk-adaptive therapies.

Keywords: circulating tumor DNA (ctDNA); gene mutation; lymphoma; next-generation sequencing (NGS); prognosis; tumor heterogeneity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Numbers of ctDNA and gDNA mutations. There were 52 mutations in ctDNA and 74 mutations in gDNA, 44 mutations were common to them.
Figure 2
Figure 2
Distribution of lymphoma subtypes. Distribution of pathological subtypes and genetic alterations of ctDNA in the total cohort. (A) Detailed distribution of pathological subtypes of 59 lymphomas. (B) Genetic alterations of ctDNA in the total cohort. HL, Hodgkin’s lymphoma; DLBCL, diffuse large B cell lymphoma; MZL, marginal zone lymphoma.
Figure 3
Figure 3
Distribution of mutation allele frequencies and the pathways in lymphoma patients. (A) Mutation allele frequencies and the pathways in HL; (B) Mutation allele frequencies and the pathways in GCB; (C) Mutation allele frequencies and the pathways in non-GCB; (D) Mutation allele frequencies and the pathways in MZL.
Figure 4
Figure 4
Progression-free survival curves of patients with lymphoma. Kaplan-Meier curves for progression-free survival by presence or absence of genes mutation. (A–I) was genes: MYD88, FAT1, MALT1, ROS1, TBL1XR1, CREBBP, KMT2D, TET2, and TRAF3. (J) was the progression-free survival curve for all patients.
See this image and copyright information in PMC

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