Background: BCL6 translocations (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 fusions were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 fusions. Consequently, the BCL6 translocation pattern is a potential prognostic indicator. Methods: A total of 21 DLBCL patients were enrolled in the study. Target-captured next generation sequencing was performed on circulating tumor DNA or tumor tissue genomic DNA, which enables simultaneously assess somatic single-nucleotide variants, insertions/deletions and copy-number alterations across 612 genes, and detects rearrangements across 35 genes. Results: In total, we identified 251 genetic alterations with a median of 10 (1-33) mutations per patient. PCLO (33.3%), TP53 (23.8%) and PRDM1 (23.8%) were commonly mutated in DLBCL. The manifest frequent mutations in TP53, CD79B (14.3%), CREBBP (14.3%), ATM (9.5%) and MYD88 (9.5%) for which there currently exist potential targeted therapies. 47.6% (10/21) of patients exhibit gene rearrangements, including BCL6, BCL2, ALK and MLL. 33.3% (7/21) of patients acquired BCL6 translocations. Three patients (42.9%) were Ig/BCL6 fusions, the partner gene of non-Ig/BCL6 fusions patients was EIF4A2, IKZF1, HIST1H4I, respectively (Table 1). Conclusions: Target-captured next-generation sequencing can be used to discover the BCL6 gene breakpoints and partner gene in DLBCL.Table 1