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574 results on '"Wlodarska, Iwona"'

1. The landscape of copy number variations in classical Hodgkin lymphoma: a joint KU Leuven and LYSA study on cell-free DNA

Author

Buedts, Lieselot, Wlodarska, Iwona, Finalet-Ferreiro, Julio, Gheysens, Olivier, Dehaspe, Luc, Tousseyn, Thomas, Fornecker, Luc-Matthieu, Lazarovici, Julien, Casasnovas, René-Olivier, Gac, Anne-Claire, Bonnet, Christophe, Bouabdallah, Kamal, Copie-Bergman, Christiane, Fabiani, Bettina, Dierickx, Daan, Marcelis, Lukas, Vermeesch, Joris, André, Marc, and Vandenberghe, Peter

Published
2021
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4. Cytogenetics

Author

Raca, Gordana, van der Krogt, Jo-Anne, Le Beau, Michelle M., Wlodarska, Iwona, Dreyling, Martin, editor, and Williams, Michael E., editor

Published
2014
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6. Non-invasive detection of genomic imbalances in Hodgkin/Reed-Sternberg cells in early and advanced stage Hodgkin's lymphoma by sequencing of circulating cell-free DNA: a technical proof-of-principle study

Author

Vandenberghe, Peter, Wlodarska, Iwona, Tousseyn, Thomas, Dehaspe, Luc, Dierickx, Daan, Verheecke, Magali, Uyttebroeck, Anne, Bechter, Oliver, Delforge, Michel, Vandecaveye, Vincent, Brison, Nathalie, Verhoef, Gregor EG, Legius, Eric, Amant, Frederic, and Vermeesch, Joris R

Published
2015
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8. Primary mediastinal large B‐cell lymphoma is characterized by large‐scale copy‐neutral loss of heterozygosity

Author

Tuveri, Stefania, primary, Debackere, Koen, additional, Marcelis, Lukas, additional, Dierckxsens, Nicolas, additional, Demeulemeester, Jonas, additional, Dimitriadou, Eftychia, additional, Dierickx, Daan, additional, Lefesvre, Pierre, additional, Deraedt, Karen, additional, Graux, Carlos, additional, Michaux, Lucienne, additional, Cools, Jan, additional, Tousseyn, Thomas, additional, Vermeesch, Joris Robert, additional, and Wlodarska, Iwona, additional

Published
2022
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9. Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Tuveri, Stefania, Debackere, Koen, Marcelis, Lukas, Dierckxsens, Nicolas, Demeulemeester, Jonas, Dimitriadou, Eftychia, Dierickx, Daan, Lefesvre, Pierre, Deraedt, Karen, Graux, Carlos, Michaux, Lucienne, Cools, Jan, Tousseyn, Thomas, Vermeesch, Joris Robert, Wlodarska, Iwona, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Tuveri, Stefania, Debackere, Koen, Marcelis, Lukas, Dierckxsens, Nicolas, Demeulemeester, Jonas, Dimitriadou, Eftychia, Dierickx, Daan, Lefesvre, Pierre, Deraedt, Karen, Graux, Carlos, Michaux, Lucienne, Cools, Jan, Tousseyn, Thomas, Vermeesch, Joris Robert, and Wlodarska, Iwona

Abstract

Development of primary mediastinal B-cell lymphoma (PMBL) is driven by cumulative genomic aberrations. We discovered a unique copy-neutral loss of heterozygosity (CN-LOH) landscape of PMBL which distinguishes this tumor from other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma. Using single nucleotide polymorphism array analysis we identified large-scale CN-LOH lesions in 91% (30/33) of diagnostic PMBLs and both investigated PMBL-derived cell lines. Altogether, the cohort showed 157 extra-large (25.3-248.4 Mb) CN-LOH lesions affecting up to 14 chromosomes per case (mean of 4.4) and resulting in a reduction of heterozygosity an average of 9.9% (range 1.3-51%) of the genome. Predominant involvement of terminal chromosomal segments suggests the implication of B-cell specific crossover events in the pathogenesis of PMBL. Notably, CN-LOH stretches non-randomly clustered on 6p (60%), 15 (37.2%), and 17q (40%), and frequently co-occurred with homozygous mutations in the MHC I (6p21), B2M (15q15), and GNA13 (17q23) genes, respectively, as shown by preliminary whole-exome/genome sequencing data. Altogether, our findings implicate CN-LOH as a novel and distinct mutational process contributing to the molecular pathogenesis of PMBL. The aberration acting as "second hit" in the Knudson hypothesis, ranks as the major mechanism converting to homozygosity the PMBL-related driver genes. Screening of the cohort of 199 B cell leukemia/lymphoma whole-genomes revealed significant differences in the CN-LOH landscape of PMBL and other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma.

Published
2022

10. Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity

Author

Tuveri, Stefania, Debackere, Koenraad, Marcelis, Lukas, Dierckxsens, Nicolas, Demeulemeester, Jonas, Dimitriadou, Eftychia, Dierickx, Daan, Lefesvre, Pierre, Deraedt, Karen, Graux, Carlos, Michaux, Lucienne, Cools, Jan, Tousseyn, Thomas, Vermeesch, Joris Robert, Wlodarska, Iwona, Tuveri, Stefania, Debackere, Koenraad, Marcelis, Lukas, Dierckxsens, Nicolas, Demeulemeester, Jonas, Dimitriadou, Eftychia, Dierickx, Daan, Lefesvre, Pierre, Deraedt, Karen, Graux, Carlos, Michaux, Lucienne, Cools, Jan, Tousseyn, Thomas, Vermeesch, Joris Robert, and Wlodarska, Iwona

Abstract

Development of primary mediastinal B-cell lymphoma (PMBL) is driven by cumulative genomic aberrations. We discovered a unique copy-neutral loss of heterozygosity (CN-LOH) landscape of PMBL which distinguishes this tumor from other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma. Using single nucleotide polymorphism array analysis we identified large-scale CN-LOH lesions in 91% (30/33) of diagnostic PMBLs and both investigated PMBL-derived cell lines. Altogether, the cohort showed 157 extra-large (25.3–248.4 Mb) CN-LOH lesions affecting up to 14 chromosomes per case (mean of 4.4) and resulting in a reduction of heterozygosity an average of 9.9% (range 1.3–51%) of the genome. Predominant involvement of terminal chromosomal segments suggests the implication of B-cell specific crossover events in the pathogenesis of PMBL. Notably, CN-LOH stretches non-randomly clustered on 6p (60%), 15 (37.2%), and 17q (40%), and frequently co-occurred with homozygous mutations in the MHC I (6p21), B2M (15q15), and GNA13 (17q23) genes, respectively, as shown by preliminary whole-exome/genome sequencing data. Altogether, our findings implicate CN-LOH as a novel and distinct mutational process contributing to the molecular pathogenesis of PMBL. The aberration acting as “second hit” in the Knudson hypothesis, ranks as the major mechanism converting to homozygosity the PMBL-related driver genes. Screening of the cohort of 199 B cell leukemia/lymphoma whole-genomes revealed significant differences in the CN-LOH landscape of PMBL and other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Published
2022

13. Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group

Author

Salido, Marta, Baró, Cristina, Oscier, David, Stamatopoulos, Kostas, Dierlamm, Judith, Matutes, Estela, Traverse-Glehen, Alexandra, Berger, Francoise, Felman, Pascale, Thieblemont, Catherine, Gesk, Stefan, Athanasiadou, Anastasia, Davis, Zadie, Gardiner, Anne, Milla, Fuensanta, Ferrer, Ana, Mollejo, Manuela, Calasanz, Maria José, Florensa, Lourdes, Espinet, Blanca, Luño, Elisa, Wlodarska, Iwona, Verhoef, Gregor, García-Granero, Marta, Salar, Antonio, Papadaki, Theodora, Serrano, Sergio, Piris, Miguel A., and Solé, Francesc

Published
2010
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16. Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing

Author

Amant, Frédéric, Verheecke, Magali, Wlodarska, Iwona, Dehaspe, Luc, Brady, Paul, Brison, Nathalie, Van Den Bogaert, Kris, Dierickx, Daan, Vandecaveye, Vincent, Tousseyn, Thomas, Moerman, Philippe, Vanderstichele, Adriaan, Vergote, Ignace, Neven, Patrick, Berteloot, Patrick, Putseys, Katrien, Danneels, Lode, Vandenberghe, Peter, Legius, Eric, and Vermeesch, Joris Robert

Published
2015
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18. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia

Author

De Keersmaecker, Kim, Atak, Zeynep Kalender, Li, Ning, Vicente, Carmen, Patchett, Stephanie, Girardi, Tiziana, Gianfelici, Valentina, Geerdens, Ellen, Clappier, Emmanuelle, Porcu, Michaël, Lahortiga, Idoya, Lucà, Rossella, Yan, Jiekun, Hulselmans, Gert, Vranckx, Hilde, Vandepoel, Roel, Sweron, Bram, Jacobs, Kris, Mentens, Nicole, Wlodarska, Iwona, Cauwelier, Barbara, Cloos, Jacqueline, Soulier, Jean, Uyttebroeck, Anne, Bagni, Claudia, Hassan, Bassem A, Vandenberghe, Peter, Johnson, Arlen W, Aerts, Stein, and Cools, Jan

Published
2013
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20. The landscape of copy number variations in classical Hodgkin lymphoma: a joint KU Leuven and LYSA study on cell-free DNA.

Author

UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Buedts, Lieselot, Wlodarska, Iwona, Finalet-Ferreiro, Julio, Gheysens, Olivier, Dehaspe, Luc, Tousseyn, Thomas, Fornecker, Luc-Matthieu, Lazarovici, Julien, Casasnovas, René-Olivier, Gac, Anne-Claire, Bonnet, Christophe, Bouabdallah, Kamal, Copie-Bergman, Christiane, Fabiani, Bettina, Dierickx, Daan, Marcelis, Lukas, Vermeesch, Joris, André, Marc, Vandenberghe, Peter, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Buedts, Lieselot, Wlodarska, Iwona, Finalet-Ferreiro, Julio, Gheysens, Olivier, Dehaspe, Luc, Tousseyn, Thomas, Fornecker, Luc-Matthieu, Lazarovici, Julien, Casasnovas, René-Olivier, Gac, Anne-Claire, Bonnet, Christophe, Bouabdallah, Kamal, Copie-Bergman, Christiane, Fabiani, Bettina, Dierickx, Daan, Marcelis, Lukas, Vermeesch, Joris, André, Marc, and Vandenberghe, Peter

Abstract

The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p14 (50%), 12q13 (50%), 9p24 (50%), 5q (44%), 17q (43%), 2q (41%). Losses mostly affected 13q (57%), 6q25-q27 (55%), 4q35 (50%), 11q23 (44%), 8p21 (43%). In addition, we identified loss of 3p13-p26 and of 12q21-q24 and gain of 15q21-q26 as novel recurrent CNAs in cHL. At diagnosis, ctDNA concentration was associated with advanced disease, male sex, extensive nodal disease, elevated erythrocyte sedimentation rate, metabolic tumor volume, and HRS cell burden. CNAs and ctDNA rapidly diminished upon treatment initiation, and persistence of CNAs was associated with increased probability of relapse. This study endorses the development of ctDNA as gateway to the HRS genome and substrate for early disease response evaluation.

Published
2021

21. Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Debackere, Koen, Marcelis, Lukas, Demeyer, Sofie, Vanden Bempt, Marlies, Mentens, Nicole, Gielen, Olga, Jacobs, Kris, Broux, Michael, Verhoef, Gregor, Michaux, Lucienne, Graux, Carlos, Wlodarska, Iwona, Gaulard, Philippe, de Leval, Laurence, Tousseyn, Thomas, Cools, Jan, Dierickx, Daan, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Debackere, Koen, Marcelis, Lukas, Demeyer, Sofie, Vanden Bempt, Marlies, Mentens, Nicole, Gielen, Olga, Jacobs, Kris, Broux, Michael, Verhoef, Gregor, Michaux, Lucienne, Graux, Carlos, Wlodarska, Iwona, Gaulard, Philippe, de Leval, Laurence, Tousseyn, Thomas, Cools, Jan, and Dierickx, Daan

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.

Published
2021

22. Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course

Author

Put, Natalie, Van Roosbroeck, Katrien, Konings, Peter, Meeus, Peter, Brusselmans, Caroline, Rack, Katrina, Gervais, Carine, Nguyen-Khac, Florence, Chapiro, Elise, Radford-Weiss, Isabelle, Struski, Stéphanie, Dastugue, Nicole, Gachard, Nathalie, Lefebvre, Christine, Barin, Carole, Eclache, Virginie, Fert-Ferrer, Sandra, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Quilichini, Benoît, Poirel, Hélène A., Wlodarska, Iwona, Hagemeijer, Anne, Moreau, Yves, Vandenberghe, Peter, Michaux, Lucienne, and on behalf of the BCGHo and the GFCH

Published
2012
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24. GATA4 Mutations Are a Cause of Neonatal and Childhood-Onset Diabetes

Author

Shaw-Smith, Charles, De Franco, Elisa, Lango Allen, Hana, Batlle, Marta, Flanagan, Sarah E., Borowiec, Maciej, Taplin, Craig E., van Alfen-van der Velden, Janiëlle, Cruz-Rojo, Jaime, Perez de Nanclares, Guiomar, Miedzybrodzka, Zosia, Deja, Grazyna, Wlodarska, Iwona, Mlynarski, Wojciech, Ferrer, Jorge, Hattersley, Andrew T., and Ellard, Sian

Published
2014
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27. FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T cell lymphoma, not otherwise specified

Author

Debackere, Koen, primary, Marcelis, Lukas, additional, Demeyer, Sofie, additional, Bempt, Marlies Vanden, additional, Mentens, Nicole, additional, Gielen, Olga, additional, Jacobs, Kris, additional, Broux, Michael, additional, Verhoef, Gregor, additional, Michaux, Lucienne, additional, Graux, Carlos, additional, Wlodarska, Iwona, additional, Gaulard, Philippe, additional, de Leval, Laurence, additional, Tousseyn, Thomas, additional, Cools, Jan, additional, and Dierickx, Daan, additional

Published
2021
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28. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome

Author

Cools, Jan, DeAngelo, Daniel J., Gotlib, Jason, Stover, Elizabeth H., Legare, Robert D., Cortes, Jorges, Kutok, Jeffrey, Clark, Jennifer, Galinsky, Ilene, Griffin, James D., Cross, Nicholas C.P., Tefferi, Ayalew, Malone, James, Alam, Rafeul, Schrier, Stanley L., Schmid, Janet, Rose, Michal, Vandenberghe, Peter, Verhoef, Gregor, Boogaerts, Marc, Wlodarska, Iwona, Kantarjian, Hagop, Marynen, Peter, Coutre, Steven E., Stone, Richard, and Gilliland, D. Gary

Subjects
Gleevec (Medication) -- Evaluation, Eosinophilia -- Drug therapy, Eosinophilia -- Causes of
Abstract

Some patients with hypereosinophilic syndrome may have a chromosome abnormality similar to the one that causes chronic myeloid leukemia. The abnormality produces a defective enzyme that stimulates an overproduction of blood cells. This was confirmed by a study of 11 patients with hypereosinophilic syndrome, nine of whom were successfully treated with the drug Gleevec. Gleevec inhibits the defective enzyme and has been used to treat chronic myeloid leukemia.

Published
2003

31. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Author

Duhoux, Francois P., Ameye, Geneviève, Montano-Almendras, Carmen P., Bahloula, Khadija, Mozziconacci, Marie J., Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Auger, Nathalie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Roche-Lestienne, Catherine, Latinne, Dominique, Libouton, Jeanne M., Demoulin, Jean-Baptiste, and Poirel, Hélène A.

Published
2012
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32. FER and FES tyrosine kinase fusions in follicular T-cell lymphoma

Author

Debackere, Koen, primary, van der Krogt, Jo-Anne, primary, Tousseyn, Thomas, primary, Ferreiro, Julio Antonio Finalet, primary, Van Roosbroeck, Katrien, primary, Marcelis, Lukas, primary, Graux, Carlos, primary, Dierickx, Daan, primary, Ameye, Geneviève, primary, Vandenberghe, Peter, primary, Michaux, Lucienne, primary, Cools, Jan, primary, and Wlodarska, Iwona, primary

Published
2020
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33. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis

Author

Levine, Ross L., Wadleigh, Martha, Cools, Jan, Ebert, Benjamin L., Wernig, Gerlinde, Huntly, Brian J.P., Boggon, Titus J., Wlodarska, Iwona, Clark, Jennifer J., Moore, Sandra, Adelsperger, Jennifer, Koo, Sumin, Lee, Jeffrey C., Gabriel, Stacey, Mercher, Thomas, D’Andrea, Alan, Fröhling, Stefan, Döhner, Konstanze, Marynen, Peter, Vandenberghe, Peter, Mesa, Ruben A., Tefferi, Ayalew, Griffin, James D., Eck, Michael J., Sellers, William R., Meyerson, Matthew, Golub, Todd R., Lee, Stephanie J., and Gilliland, D. Gary

Published
2005
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41. BCL6 gene rearrangements also occur in marginal zone B-cell lymphoma

Author

Dierlamm, Judith, Pittaluga, Stefania, Stul, Michel, Wlodarska, Iwona, Michaux, Lucienne, Thomas, Jose, Verhoef, Gregor, Verhest, Alain, Depardieu, Claude, Cassiman, Jean-Jacques, Hagemeijer, Anne, De Wolf-Peeters, Christiane, and Van den Berghe, Herman

Published
1997

42. SEC31A-ALK Fusion Gene in Lung Adenocarcinoma

Author

Kim, Ryong Nam, Choi, Yoon-La, Lee, Mi-Sook, Lira, Maruja E, Mao, Mao, Mann, Derrick, Stahl, Joshua, Licon, Abel, Choi, So Jung, Van Vrancken, Michael, Han, Joungho, Wlodarska, Iwona, and Kim, Jhingook

Subjects
Male, Lung Neoplasms, Genetic translocation, Oncogene Proteins, Fusion, Vesicular Transport Proteins, Receptor Protein-Tyrosine Kinases, Case Report, Exons, Adenocarcinoma, Middle Aged, Anaplastic lymphoma kinase, hemic and lymphatic diseases, Humans, Oncogene Fusion, SEC31A, In Situ Hybridization, Fluorescence
Abstract

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to generation of an intact, in-frame open reading frame. SEC31A-ALK encodes a predicted fusion protein of 1438 amino acids comprising the WD40 domain of SEC31A at the N-terminus and ALK kinase domain at the C-terminus. FISH studies suggested that SEC31A-ALK was generated by an unbalanced genomic rearrangement associated with loss of the 3'end of SEC31A. This is the first report of SEC31A-ALK fusion transcript in clinical NSCLC, which could be a novel diagnostic and therapeutic target for patients with NSCLC. ispartof: Cancer Research and Treatment vol:48 issue:1 pages:398-402 ispartof: location:Korea (South) status: published

Published
2015

47. ALK-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene

Author

van de Krogt, Jo-Anne, Vanden Bempt, Marlies, Finalet Ferreiro, Julio, Mentens, Nicole, Jacobs, Kris, Pluys, Ursula, Doms, Kathleen, Geerdens, Ellen, Uyttebroeck, Anne, Pierre, Pascal, Michaux, Lucienne, Devos, Timothy, Vandenberghe, Peter, Tousseyn, Thomas, Cools, Jan, and Wlodarska, Iwona

Subjects
hemic and lymphatic diseases
Abstract

ALK positive anaplastic large cell lymphoma is characterized by 2p23/ALK aberrations, including the classic t(2;5)(p23;q35)/NPM1-ALK rearrangement present in ~80% of cases and several variant t(2p23/ALK) occurring in the remaining cases. The ALK fusion partners play a key role in the constitutive activation of the chimeric protein and its subcellular localization. Using various molecular technologies, we have characterized ALK fusions in eight recently diagnosed anaplastic large cell lymphoma cases with cytoplasmic-only ALK expression. The identified partner genes included EEF1G (one case), RNF213/ALO17 (one case), ATIC (four cases) and TPM3 (two cases). Notably, all cases showed copy number gain of the rearranged ALK gene, which is never observed in NPM1-ALK-positive lymphomas. We hypothesized that this could be due to lower expression levels and/or lower oncogenic potential of the variant ALK fusions. Indeed, all partner genes, except EEF1G, showed lower expression in normal and malignant T cells, in comparison with NPM1. In addition, we investigated the transformation potential of endogenous Npm1-Alk and Atic-Alk fusions generated by CRISPR/Cas9 genome editing in Ba/F3 cells. We found that Npm1-Alk has a stronger transformation potential than Atic-Alk, and we observed a subclonal gain of Atic-Alk after a longer culture period, which was not observed for Npm1-Alk. Taken together, our data illustrate that lymphomas driven by the variant ATIC-ALK fusion (and likely by RNF213-ALK, and TPM3-ALK), but not the classic NPM1-ALK, require an increased dosage of the ALK hybrid gene to compensate for the relatively low and insufficient expression and signaling properties of the chimeric gene. ispartof: Haematologica vol:102 issue:9 pages:1605-1616 ispartof: location:Italy status: published

Published
2017

48. Novel GPR34 and CCR6 mutation and distinct genetic profiles in MALT lymphomas of different sites

Author

Moody, Sarah, primary, Thompson, Joe Sneath, additional, Chuang, Shih-Sung, additional, Liu, Hongxiang, additional, Raderer, Markus, additional, Vassiliou, George, additional, Wlodarska, Iwona, additional, Wu, Fangtian, additional, Cogliatti, Sergio, additional, Robson, Alistair, additional, Ashton-Key, Margaret, additional, Bi, Yingwen, additional, Goodlad, John, additional, and Du, Ming-Qing, additional

Published
2018
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50. Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies

Author

Van Roosbroeck, Katrien, Finalet Ferreiro, Julio, Tousseyn, Thomas, van der Krogt, Jo-Anne, Michaux, Lucienne, Pienkowska-Grela, Barbara, Theate, Ivan, De Paepe, Pascale, Dierickx, Daan, Doyen, Chantal, Put, Natalie, Cools, Jan, Vandenberghe, Peter, and Wlodarska, Iwona

Subjects
hemic and lymphatic diseases
Abstract

The recurrent 9p24.1 aberrations in lymphoid malignancies potentially involving four cancer-related and druggable genes (JAK2, CD274/PDL1, PDCD1LG2/PDL2, and KDM4C/JMJD2Cl) are incompletely characterized. To gain more insight into the anatomy of these abnormalities, at first we studied 9p24.1 alterations in 18 leukemia/lymphoma cases using cytogenetic and molecular techniques. The aberrations comprised structural (nine cases) and numerical (nine cases) alterations. The former lesions were heterogeneous but shared a common breakpoint region of 200 kb downstream of JAK2. The rearrangements predominantly targeted the PDL locus. We have identified five potential partner genes of PDL1/2: PHACTR4 (1p34), N4BP2 (4p14), EEF1A1 (6q13), AK2 (9p24.1), and IGL (22q11). Interestingly, the cryptic JAK2-PDL1 rearrangement was generated by a microdeletion spanning the 3'JAK2-5'PDL1 region. JAK2 was additionally involved in a cytogenetically cryptic IGH-mediated t(9;14)(p24.1;q32) found in two patients. This rare but likely underestimated rearrangement highlights the essential role of JAK2 in B-cell neoplasms. Cases with amplification of 9p24.1 were diagnosed as primary mediastinal B-cell lymphoma (five cases) and T-cell lymphoma (four cases). The smallest amplified 9p24.1 region was restricted to the JAK2-PDL1/2-RANBP6 interval. In the next step, we screened 200 cases of classical Hodgkin lymphoma by interphase FISH and identified PDL1/2 rearrangement (CIITA- and IGH-negative) in four cases (2%), what is a novel finding. Forty (25%) cases revealed high level amplification of 9p24.1, including four cases with a selective amplification of PDL1/2. Altogether, the majority of 9p24.1 rearrangements occurring in lymphoid malignancies seem to target the programmed death-1 ligands, what potentiates the therapeutic activity of PD-1 blockade in these tumors. © 2016 Wiley Periodicals, Inc. ispartof: Genes, Chromosomes & Cancer vol:55 issue:5 pages:428-441 ispartof: location:United States status: published

Published
2016

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