Differences between BCL2-break positive and negative follicular lymphoma unraveled by whole-exome sequencing

A. Zamò, J. Pischimarov, M. Schlesner, P. Rosenstiel, R. Bomben, H. Horn, T. Grieb, T. Nedeva, C. López, A. Haake, J. Richter, L. Trümper, C. Lawerenz, W. Klapper, P. Möller, M. Hummel, D. Lenze, M. Szczepanowski, L. Flossbach, M. SchrederV. Gattei, G. Ott, R. Siebert, A. Rosenwald, E. Leich

Research output: Contribution to journalArticlepeer-review


Depending on disease stage follicular lymphoma (FL) lack the t(14;18) in ∼15-∼50% of cases. Nevertheless, most of these cases express BCL2. To elucidate mechanisms triggering BCL2 expression and promoting pathogenesis in t(14;18)-negative FL, exonic single-nucleotide variant (SNV) profiles of 28 t(14;18)-positive and 13 t(14;18)-negative FL were analyzed, followed by the integration of copy-number changes, copy-neutral LOH and published gene-expression data as well as the assessment of immunoglobulin N-glycosylation sites. Typical FL mutations also affected t(14;18)-negative FL. Curated gene set/pathway annotation of genes mutated in either t(14;18)-positive or t(14;18)-negative FL revealed a strong enrichment of same or similar gene sets but also a more prominent or exclusive enrichment of immune response and N-glycosylation signatures in t(14;18)-negative FL. Mutated genes showed high BCL2 association in both subgroups. Among the genes mutated in t(14;18)-negative FL 555 were affected by copy-number alterations and/or copy-neutral LOH and 96 were differently expressed between t(14;18)-positive and t(14;18)-negative FL (P<0.01). N-glycosylation sites were detected considerably less frequently in t(14;18)-negative FL. These results suggest a diverse portfolio of genetic alterations that may induce or regulate BCL2 expression or promote pathogenesis of t(14;18)-negative FL as well as a less specific but increased crosstalk with the microenvironment that may compensate for the lack of N-glycosylation.

Original languageEnglish
Pages (from-to)685-693
Number of pages9
Issue number3
Publication statusPublished - Mar 1 2018

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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