BTG1 Mutation Correlates with Inferior Prognosis in Diffuse Large B-Cell Lymphoma.

PURPOSE: B-cell translocation gene 1 (BTG1) is a highly conserved gene and recurrently mutated in the MCD subtype of diffuse large B-cell lymphoma (DLBCL). The specific enrichment of BTG1 mutation (BTG1mut) raises a potential hypothesis that they may actively contribute to DLBCL. However, the biological characteristics and prognostic signifi cance ofBTG1 in DLBCL remain to be explored. Therefore, the objective of our study was to evaluate the value of BTG1 in DLBCL.

MATERIALS AND

METHODS

The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Tumor tissue samples of DLBCL patients diagnosed in Jiangsu Province Hospital (JSPH) from 2021 to 2023 were collected for next-generation sequencing, 195 samples were analyzed for gene expression levels using RNA sequencing, among them, 40 samples were analyzed by untargeted metabolomics.

RESULTS

We enrolled 2,379 DLBCL patients from fi ve published studies and 243 DLBCL patients from JSPH cohort. In external cohort, 11.0% (262/2,379) of patients were BTG1mut, compared with 25.1% (61/243) in the JSPH cohort. BTG1mut was associated with adverse clinical features and was prone to involve testis. Patients with BTG1mut exhibit inferior overall survival. Furthermore, pathway enrichment analysis of the untargeted metabolomics showed that several meaningful pathways have been found such as amino acid metabolism and lipid metabolism.

CONCLUSION

BTG1 mutation was promising prognostic predictor for DLBCL. The mechanism driving different survival outcomes may be attributed to the tumor metabolic reprogramming.