Proceedings/Recueil Des Communications European Journal of Human Genetics Année : 2024

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

Résumé

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.

Dates et versions

hal-05042510 , version 1 (22-04-2025)

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Emil Chteinberg, Gioia Di Stefano, Henry Löffler-Wirth, Annette M. Staiger, Sina Hillebrecht, et al.. Deciphering the Gene Expression Signature of High-Grade B-cell Lymphomas with 11q Aberrations. 57th European Society of Human Genetics (ESHG) Conference, Jun 2024, Berlin, Germany. European Journal of Human Genetics, 32 (S2), SPRINGERNATURE, pp.1231-1841, 2024, ⟨10.1038/s41431-024-01734-4⟩. ⟨hal-05042510⟩
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