Background: Burkitt lymphoma/leukemia (BL/BAL) is the most common lymphoma in chidren and sporadic subtype is dominant in Chinese population. MYC gene translocation is essential for sporadic BL/BAL (sBL/BAL), whereas other gene mutations also play important roles in the development of sBL/BAL.
Methods: The clinical data of ten Chinese children with sBL/BAL were collected; next generation sequencing of tumor tissues were detected. BL and diffused large B cell lymphoma (DLBCL) database was also collected and bioinformatics analyzed was done.
Results: Nine male and one female were enrolled in the study, including six BL patients (stage III) and four BAL patients (stage IV). Average age at diagnosis was 100.10±13.39mon; overexpression of CD20 was detectable, MYC rearrangement were confirmed. The patients received combination treatment of chemotherapy and Rituximab, complete remission was achieved and all the patients survived. Germline causal gene mutations were detected in four (40%) patients by whole exome sequencing (WES); ID3, BRCA2, ARID1A and SMARCA4 mutations, except MYC mutation, were the most common somatic mutations. The gene functions in pathopoiesis were differ from BL to DLBCL in dataset. These identified mutated genes were enriched and connected by GO or KEGG pathway, it seemed that PI3K-Akt signaling pathway or EGFR-TKI resistance pathway play important roles in the pathopoiesis of sBL/BAL.
Conclusion: sBL/BAL is a highly aggressive but curable lymphoma; the pathophysiolopoiesis is still in research. The molecular hallmark of sBL/BAL is MYC translocation, whereas additional chromosomal abnormalities and gene mutations also occur and play roles in the progression of the disease. PI3K-Akt signaling pathway seems play important roles in the pathopoiesis of sBL/BAL, and sBL/BAL may be inhibited by such signaling pathway; EGFR-TKI resistance pathway was also analyzed in sBL/BAL patients, it reveals that EGFR-TKI treatment is invalid. Further research is needed for the hypothesis and possible mechanisms.