Zhang Jing, Meng Leijun, Jiang Weiyun, Zhang Hong, Zhou Aiwu, Zeng Naiyan
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.
Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai 200040, China.
Transl Oncol. 2020 Dec;13(12):100855. doi: 10.1016/j.tranon.2020.100855. Epub 2020 Sep 15.
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.
伯基特淋巴瘤（BL）是儿童中的一种恶性肿瘤。尽管BL通常可治愈，但可能会出现早期复发和难治性情况。最近已提出一些分子指标用于BL诊断，但仍存在很大的异质性。本研究旨在提供可能有助于改善儿童BL诊断和治疗的临床分子靶点及方法。该研究仅纳入儿童患者，并进行靶向基因测序以鉴定肿瘤特异性突变。通过实时PCR和免疫组织化学检测潜在靶基因的mRNA和蛋白质水平表达。分析了BL特异性基因突变和差异表达与临床特征之间的关系。结果表明：i）对c-MYC/BCL2/BCL6基因位点改变和基因表达进行详细分析有助于儿童BL的准确诊断和治疗决策；ii）SOCS1或CIITA基因的功能丧失突变可能用作BL诊断和预后的恶性标志物；iii）CD79A、MYD88、KLF2、DNMT3A和NFKBIE基因的特异性突变在BL中常同时存在，并与良好的临床结果相关；iv）肿瘤中MYC、TCF3的高表达和功能丧失的ID3基因可能是潜在的治疗靶点，可用于治疗监测；v）4例MYC易位阴性病例被重新定义为高级别B细胞淋巴瘤，非特指型（HGBL-NOS），但在该研究中显示出与其他BL病例相似的临床结果和分子特征，这表明需要更多研究来探索这种临时肿瘤实体的分子机制和临床意义。
