학술논문
Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
Document Type
Original Paper
Author
Kalmbach, Sabrina; Grau, Michael; Zapukhlyak, Myroslav; Leich, Ellen; Jurinovic, Vindi; Hoster, Eva; Staiger, Annette M.; Kurz, Katrin S.; Weigert, Oliver; Gaitzsch, Erik; Passerini, Verena; Engelhard, Marianne; Herfarth, Klaus; Beiske, Klaus; Micci, Francesca; Möller, Peter; Bernd, Heinz-Wolfram; Feller, Alfred C.; Klapper, Wolfram; Stein, Harald; Hansmann, Martin-Leo; Hartmann, Sylvia; Dreyling, Martin; Holte, Harald; Lenz, Georg; Rosenwald, Andreas; Ott, German; Horn, Heike
Source
Leukemia. 37(10):2058-2065
Subject
Language
English
ISSN
0887-6924
1476-5551
1476-5551
Abstract
Knowledge on the pathogenesis of FL is mainly based on data derived from advanced/systemic stages of FL (sFL) and only small cohorts of localized FL (lFL) have been characterized intensively so far. Comprehensive analysis with profiling of somatic copy number alterations (SCNA) and whole exome sequencing (WES) was performed in 147 lFL and 122 sFL. Putative targets were analyzed for gene and protein expression. Overall, lFL and sFL, as well as BCL2 translocation-positive (BCL2+) and –negative (BCL2−) FL showed overlapping features in SCNA and mutational profiles. Significant differences between lFL and sFL, however, were detected for SCNA frequencies, e.g., in 18q-gains (14% lFL vs. 36% sFL; p = 0.0003). Although rare in lFL, gains in 18q21 were associated with inferior progression-free survival (PFS). The mutational landscape of lFL and sFL included typical genetic lesions. However, ARID1A mutations were significantly more often detected in sFL (29%) compared to lFL (6%, p = 0.0001). In BCL2 + FL mutations in KMT2D, BCL2, ABL2, IGLL5 and ARID1A were enriched, while STAT6 mutations more frequently occurred in BCL2- FL. Although the landscape of lFL and sFL showed overlapping features, molecular profiling revealed novel insights and identified gains in 18q21 as prognostic marker in lFL.