Document Type

Article

Publication Date

10-13-2026

Identifier

DOI: 10.1182/bloodadvances.2026019675

Abstract

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms, including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using formalin-fixed paraffin-embedded tissues from 159 patients with DLBCL, identifying 746 cancer genes at or proximal to the rearrangement breakpoints, with a total of 1903 occurrences. Focusing on clinically important rearrangements, Hi-C detected 102 rearrangements of MYC, BCL2, and/or BCL6 in 92 patients and revealed the fusion partners, including 25 rearrangements missed by FISH. Causes of FISH-negative results included FISH-cryptic breakpoints, complex or faint FISH signals, low percentage of FISH positivity, and issues related to tissue fixation. Moreover, in 20 patients (12.6%), Hi-C sequencing detected 22 rearrangements characteristic of other lymphoma types, including CCND1 rearrangements that could lead to reclassification as mantle cell lymphoma. Survival analysis of genome-wide rearrangements using machine learning models identified MYC, PD-L1, CCND1, BCL2, NTRK1/PRCC, RRAS, and FANCE rearrangements with significant prognostic effects in the DLBCL cohort. In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

Journal Title

Blood Adv

Volume

10

Issue

19

First Page

6828

Last Page

6844

MeSH Keywords

Humans; Lymphoma, Large B-Cell, Diffuse; Gene Rearrangement; High-Throughput Nucleotide Sequencing; In Situ Hybridization, Fluorescence; Oncogenes; Female; Male

PubMed ID

42308239

Keywords

Diffuse Large B-Cell Lymphoma; Gene Rearrangement; High-Throughput Nucleotide Sequencing; Fluorescence In Situ Hybridization; Oncogenes

Comments

Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.

Publisher's Link: https://ashpublications.org/bloodadvances/article/10/19/6828/569157/Application-of-Hi-C-sequencing-to-detect-oncogene

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