Integrated Genomic DNA/RNA Profiling vs Fluorescence in Situ Hybridization in the Detection of MYC and BCL2 (and BCL6) Rearrangements in Large B-Cell Lymphomas: Updates Amid the New WHO Classification of Lymphoid Neoplasms

Abstract

Objectives: Large B-cell lymphomas (LBCLs) are a heterogeneous group of lymphoid neoplasms whose molecular and cytogenetic profile has predictive and prognostic implications. The concept of double-hit lymphomas (DHLs) was recently updated in the fifth edition of the World Health Organization classification, with the exclusion of MYC and BCL6 rearranged tumors from the group. Now, DHLs are referred to as diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements. Fluorescence in situ hybridization (FISH) is the current gold standard for detecting rearrangements in LBCLs, but comprehensive genomic profiling (CGP) has recently been suggested to be at least as accurate as FISH in classifying these neoplasms and providing additional genetic information.

Methods: We analyzed a cohort of 131 patients in whom FISH and CGP studies were performed as part of our normal clinical workflow and compared the effectiveness of FISH and CGP in detecting these clinically relevant rearrangements.

Results: Our findings are in agreement with our previously published study, which analyzed a cohort of 69 patients, supporting our hypothesis that the best approach to maximize detection of DHLs while limiting waste seems to be a combination of CGP and MYC break-apart FISH testing, the latter to capture the presence of non-IGH::MYC events.

Conclusions: Our study supports the combined use of FISH and GCP rather than either method alone to better detect MYC and BCL2 (and BCL6) gene rearrangements.

Keywords: Comprehensive genomic profiling; Diffuse large B-cell lymphoma; Double-hit lymphoma; Fluorescence in situ hybridization; High-grade B-cell lymphoma; Large B-cell lymphoma.