Deciphering the Gene Expression Signature of High-Grade B-cell Lymphomas with 11q Aberrations

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Chteinberg, Emil | Di Stefano, Gioia | Löffler-Wirth, Henry | M. Staiger, Annette | Hillebrecht, Sina | Wagener, Rabea | Bens, Susanne | Oehl-Huber, Kathrin | Dahlum, Sonja | Abramov, Dmitriy | Burkhardt, Birgit | Louissaint, Abner | Kurz, Katrin | Horn, Heike | Mottok, Anja | Santi, Raffaella | Oschlies, Ilske | Klapper, Wolfram | Schafernak, Kristian | Zhang, Yanming | Rosenwald, Andreas | Binder, Hans | Limm, Megan | Ott, German | Leoncini, Lorenzo | Hergalant, Sebastien | Delval, Coral | Siebert, Reiner

Edité par CCSD ; SPRINGERNATURE ; Nature Publishing Group -

International audience. Background/Objectives: The 5th edition of the WHO Classification of Haematolymphoid Tumours describe disease entities defined by genetic abnormalities. For instance, the diagnosis of Burkitt lymphoma (BL) requires an IG::MYC juxtaposition, e.g. due to t(8;14)(q24;q32). Some high-grade B-cell lymphomas (HGBL) lacking the MYC translocation exhibit immunophenotypic similarities to BL but share similarities at the mutational level with diffuse large B-cell lymphomas (DLBCL). A subset of these HGBL (HGBL-11q) show characteristic chromosomal aberration defined by gains in 11q23.2-11q23.3 and losses in the 11q24.1-qter region. Here, we identify differential transcriptomic features of such HGBL-11q relative to BL and DLBCL.Methods: Gene expression profiling was conducted using the HTG EdgeSeq Pan B-Cell Lymphoma Panel using RNA obtained from formal-fixed paraffin-embedded (FFPE) tissues of 7 BL, 26 HGBL-11q, 132 DLBCL, and two reactive tonsils. The panel was verified against RNAseq data available from overlapping samples of the ICGC-MMML-Seq cohort, leaving 206 genes for subsequent clustering and DESeq2 analyses. A two-step cumulative gene expression classifier was developed to segregate HGBL-11q from BL and DLBCL.Results: Using unsupervised UMAP analysis of the 206 genes, we observed that HGBL-11q clustered apart from BLs and DLBCLs. DESeq2 revealed 48 and 38 genes differentially expressed between HGBL-11q and DLBCL or BL, respectively. A two-step classifier was trained to distinguish HGBL-11q from DLBCLs and BLs, respectively. PostHoc genomic analyses of cases classified as HGBL-11q showed two cases not yet assigned to this entity to carry typical 11q aberrations.Conclusion: Gene expression profiling of FFPE tissues was effective in identifying HGBL-11q among other mature aggressive lymphomas.

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