Application of Hi-C sequencing to detect oncogene rearrangements for diagnosis and treatment of large B-cell lymphoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood Advances
Authors: Zijun Y. Xu-Monette, Chang Wang, Dehong Wu, Alexandar Tzankov, Michael B. Møller, Carlo Visco, Eric D. Hsi, Xiaoxian Zhao, Beibei Lv, Bangchen Wang, Xin Cao, Shuna Yao, April Chiu, Karen Dybkaer, Govind Bhagat, Youli Zu, Santiago Montes-Moreno, Zenggang Pan, Leon Bernal-Mizrachi, J. Han van Krieken, William Choi, Wayne Tam, Weina Chen, Maurilio Ponzoni, Andrés J. M. Ferreri, Benjamin M. Parsons, Farzaneh Khajouei, Kristin Sikkink, Yong Li, Alex R. Hastie, Anthony D. Schmitt, Ken H. Young
Institutions: Duke Medical Center, University Hospital of Basel, Odense University Hospital, University of Verona, Mayo Clinic, Wake Forest University, Aalborg University Hospital, SSM Health Care, Saint Louis University, Methodist Hospital, Marqués de Valdecilla University Hospital, University of Colorado Denver, Radboud University Nijmegen, Radboud University Medical Center, Hong Kong Sanatorium and Hospital, Northwell Health, The University of Texas Southwestern Medical Center, Vita-Salute San Raffaele University, Gundersen Health System, Children's Mercy Hospital, Duke Cancer Institute
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W7165014555
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