5 results on '"Wlodarska, Iwona"'
Search Results
2. Primary mediastinal large B‐cell lymphoma is characterized by large‐scale copy‐neutral loss of heterozygosity
- Author
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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
- Full Text
- View/download PDF
3. Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity.
- Author
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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
4. Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity
- Author
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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
5. Genomic studies of Hodgkin lymphoma using circulating cell-free DNA.
- Author
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Wlodarska, Iwona, Buedts, Lieselot, and Vandenberghe, Peter
- Subjects
GENOMICS ,HODGKIN'S disease treatment ,CELL-free DNA ,ONCOLOGY ,DNA sequencing - Abstract
The revolutionary finding of cell free DNA (cfDNA) circulating in the bloodstream had a huge impact on the development of non-invasive prenatal testing (NIPT) (obstetrics) and liquid biopsies (oncology). The latter, combined with the sequencing of tumor DNA-containing cfDNA, have been widely applied in cancer research, demonstrating the potential of these techniques to improve prognostication and guide individualized treatment strategies. During routine NIPT analysis of more than 88,000 pregnant women performed in our institution, 14 abnormal genomic profiles suggestive of maternal tumor have been identified. Interestingly, one patient was further diagnosed with classic Hodgkin lymphoma (cHL), a tumor characterized by a low content (<2%) of neoplastic cells in tumor mass. To examine whether circulating cfDNA can be informative about genomic imbalances in neoplastic Hodgkin/Reed-Sternberg (HRS) cells, we performed a pilot study of nine prospective cHL cases. This study showed that genomic profiles of cfDNA correspond to the profiles of HRS cells. To get further insights into the genome of cHL, a large study on cfDNA from 177 prospective cHL patients was subsequently established. Based on ultra-low pass sequencing of cfDNA from this cohort, we built a comprehensive catalog of genomic abnormalities, as well as their frequencies and patterns. Besides the known recurrent imbalances, such as gain/amplification of 2p16/REL-BCL11A and 9p24/JAK2-CD274-PDCDLG2, novel recurrent abnormalities were identified in cHL. Altogether, we have provided evidence that cHL is characterized by consistent and recurrent genomic imbalances and we have shown the potential of genomic profiling of cfDNA as a novel and non-invasive tool in the diagnosis and follow up of cHL patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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