Genomic mutation profile and metabolic alterations in diffuse large B-cell lymphoma with abdominal bulky mass

Diffuse large B-cell lymphoma (DLBCL) is a tumor with significant clinical and genetic heterogeneity. DLBCL with bulky mass (≥ 7.5 cm) exhibits a negative prognostic impact. Due to the low incidence and the lack of relevant studies, the drivers and characteristic genetic mutations of DLBCL with abdominal bulky mass (DLBCL-AB) remain unclear. To explore individualized treatment strategies by analyzing genomic mutation profile and characteristic biological alterations in DLBCL-AB may help to optimize patients' prognosis. Next-generation sequencing of tumor tissues from 39 patients (29 with DLBCL-AB and 10 with common DLBCL) was performed to screen mutation profiles. Three platforms, gas chromatography-mass spectrometry (GC-MS), high-resolution liquid chromatography-mass spectrometry (LC-MS polar), and high-resolution liquid chromatography-mass spectrometry (LC-MS lipid), were used to analyze the metabolic differences in the plasma samples and screen the profiles of altered metabolic substances. Bioinformatic analysis was used to explore the correlation between key genes and characteristic metabolic changes. CD58, TP53, CCND3 and CXCR4 were potential driver genes of DLBCL-AB. ETV6 and KDM5A mutations were independent risk factors for DLBCL-AB prognosis. In addition, DLBCL-AB had unique features in the pathways of ketone body synthesis and degradation, galactose metabolism, linoleic acid metabolism, aminoacyl-tRNA biosynthesis, and exotic amino acid biosynthesis. The results of bioinformatic analysis indicated that ETV6 may be the pivotal gene involved in regulating DLBCL-AB galactose metabolism and linoleic acid metabolism and affecting patient prognosis. This study comprehensively described the changes in the genetic features and metabolic characteristics of DLBCL-AB, thereby providing a theoretical basis for the precision treatment of patients with this high-risk lymphoma.