Comparison Between Integrated Genomic DNA/RNA Profiling and Fluorescence In Situ Hybridization in the Detection of MYC, BCL-2, and BCL-6 Gene Rearrangements in Large B-Cell Lymphomas

Abstract

Objectives: To compare fluorescence in situ hybridization (FISH) and a commercially available sequencing assay for comprehensive genomic profiling (CGP) to determine the best approach to identify gene rearrangements (GRs) in large B-cell lymphomas (LBCLs).

Methods: Comparison of standard-of-care FISH assays (including a two-probe approach for MYC; break-apart and fusion probes) and an integrated genomic DNA/RNA sequencing CGP approach on a set of 69 consecutive LBCL cases.

Results: CGP detected GRs, including those involving MYC (1), BCL-2 (3), and BCL-6 (3), not detected by FISH. FISH detected non-IgH-MYC (4) and BCL-6 (2) GRs that were not detected by CGP. In four instances, standalone CGP or FISH testing would have missed a double-hit lymphoma.

Conclusions: CGP was superior to FISH in the detection of IgH-MYC rearrangements but was inferior for the detection of non-IgH-MYC rearrangements. Our study demonstrates the rationale for development of a customized approach to identify GRs in LBCLs.

Keywords: MYC; Comprehensive genomic profiling; FISH; Gene rearrangements; High-grade B-cell lymphoma; Prognosis; Sequencing.