Identification of clinical molecular targets for childhood Burkitt lymphoma

Jing Zhang; Leijun Meng; Weiyun Jiang; Hong Zhang; Aiwu Zhou; Naiyan Zeng

doi:10.1016/j.tranon.2020.100855

Identification of clinical molecular targets for childhood Burkitt lymphoma

Transl Oncol. 2020 Dec;13(12):100855. doi: 10.1016/j.tranon.2020.100855. Epub 2020 Sep 15.

Authors

Jing Zhang¹, Leijun Meng², Weiyun Jiang³, Hong Zhang², Aiwu Zhou¹, Naiyan Zeng⁴

Affiliations

¹ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai 200040, China.
³ Yu Kang Biotechnology Co., Ltd, Jiaxing 314100, Zhejiang, China.
⁴ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: zengny@shsmu.edu.cn.

Abstract

Burkitt lymphoma (BL) is a malignant tumor in children. Although BL is generally curable, early relapse and refractoriness may occur. Some molecular indicators have been recently suggested for BL diagnosis, but large heterogeneity still exists. This study aimed at providing clinical molecular targets and methods that may help improve diagnosis and treatment of childhood BL. Only children patients were included in the study, and targeted gene sequencing was conducted to identify tumor specific mutations. The mRNA and protein level expression of potential target genes were measured by real-time PCR and immunohistochemistry. The relationship between BL specific gene mutation and differential expression with clinical features was analyzed. The results showed that i) detailed analysis of c-MYC/BCL2/BCL6 gene loci alteration and gene expression would help in accurate diagnosis and treatment determination of childhood BL; ii) loss-of-function mutations in SOCS1 or CIITA gene might be used as malignant markers for BL diagnosis and prognosis; iii) specific mutations of CD79A, MYD88, KLF2, DNMT3A and NFKBIE genes often concurrently existed in BL and showed association with benign clinical outcomes; iv) the high expression of MYC, TCF3 and loss-of-function ID3 genes in tumor may be potential therapeutic targets and could be used for treatment monitoring; and v) four MYC-translocation negative cases were re-defined as high-grade B-cell lymphoma-not otherwise specified (HGBL-NOS) but showed similar clinical outcomes and molecular features to other BL cases in the study, suggesting more studies needed to explore the molecular mechanisms and clinical significance of this provisional tumor entity.

Keywords: Childhood Burkitt lymphoma; Clinical molecular target; Differential gene expression; Gene mutation; Gene translocation; Targeted gene sequencing.