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Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms

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 seque...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539171/
https://www.ncbi.nlm.nih.gov/pubmed/37563306
http://dx.doi.org/10.1038/s41375-023-01995-w
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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
author_facet 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
author_sort Kalmbach, Sabrina
collection PubMed
description 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.
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spelling pubmed-105391712023-09-30 Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms 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 Leukemia Article 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. Nature Publishing Group UK 2023-08-10 2023 /pmc/articles/PMC10539171/ /pubmed/37563306 http://dx.doi.org/10.1038/s41375-023-01995-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
title Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
title_full Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
title_fullStr Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
title_full_unstemmed Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
title_short Novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
title_sort novel insights into the pathogenesis of follicular lymphoma by molecular profiling of localized and systemic disease forms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539171/
https://www.ncbi.nlm.nih.gov/pubmed/37563306
http://dx.doi.org/10.1038/s41375-023-01995-w
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