J Cancer 2019; 10(2):323-331. doi:10.7150/jca.27615

Research Paper

Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA

Peng Sun1,2*, Cui Chen3*, Yi Xia1,2*, Yu Wang1,2, Pan-Pan Liu1,2, Xi-Wen Bi1,2, Yang W. Shao4, Qiu-Xiang Ou4, Xue Wu4, Hang Yang1,2, Man Nie1,2, Xue-Wen Zhang1,2, Zhi-Ming Li1,2✉, Wen-Qi Jiang1,2✉

1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng RD East, Guangzhou, Guangdong Province 510060, P. R. China.
2. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dong Feng RD East, Guangzhou, Guangdong Province 510060, P. R. China.
3. Department of Oncology, the First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, Guangdong Province 510080, P. R. China.
4. Geneseeq Technology Inc., 101 College Street, Suite 300, Toronto, Ontario, Canada.
*These authors contributed equally to this work.

Abstract

Background: Malignant lymphomas are a group of distinct lymphoid neoplasms, exhibiting marked diversity in biological behaviors and clinical outcomes. Liquid biopsy, such as circulating cell-free DNA (cfDNA), has recently been attempted to be used for mutation profiling of lymphomas using next-generation sequencing (NGS). However, only limited data about cfDNA are restricted in Hodgkin's lymphoma and B cell lymphoma, and there is no report in the T cell lymphoma so far.

Patient and Methods: Medical records of a total of 50 lymphoma patients were retrospectively reviewed, and cfDNA samples were analyzed by capture-based NGS targeting 390 lymphoma- and cancer- relevant genes. We sought to explore the clinical utility of cfDNA in establishing the mutation profiles of different lymphoma subtypes and analyze the correlation between cfDNA concentration and other clinical indices such as serum LDH and IPI.

Results: Somatic alterations were identified in cfDNA samples with a median of 64 variants per sample. The concentration of cfDNA in the plasma was found to be significantly correlated with the clinical indices in diffuse large B cell lymphoma (DLBCL). The genetic heterogeneity of different lymphoma subtypes was clearly observed in cfDNAs from germinal center B-cell (GCB) DLBCL, non-GCB DLBCL and natural killer/T-cell lymphoma (NKTCL), confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas.

Conclusion: Our findings demonstrate that NGS-based cfDNA mutation profiling reveals genetic heterogeneity across lymphoma subtypes, with potential implications for the discovery of therapeutic targets, the exploration of genome evolution and the development of risk-adapted treatment.

Keywords: malignant lymphoma, circulating cell-free DNA, tumor heterogeneity, next-generation sequencing (NGS), China

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How to cite this article:
Sun P, Chen C, Xia Y, Wang Y, Liu PP, Bi XW, Shao YW, Ou QX, Wu X, Yang H, Nie M, Zhang XW, Li ZM, Jiang WQ. Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA. J Cancer 2019; 10(2):323-331. doi:10.7150/jca.27615. Available from http://www.jcancer.org/v10p0323.htm