Author: "Dominique Penther" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Dominique Penther"' showing total 96 results

Start Over Author "Dominique Penther"

96 results on '"Dominique Penther"'

1. Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE

Author: Vincent Camus, Mathieu Viennot, Pierre-Julien Viailly, Fanny Drieux, Elena-Liana Veresezan, Victor Bobée, Vinciane Rainville, Elodie Bohers, Pierre Sesques, Corinne Haioun, Eric Durot, Michael Bayaram, Cédric Rossi, Laurent Martin, Dominique Penther, Sophie Kaltenbach, Julie Bruneau, Jérôme Paillassa, Olivier Tournilhac, Nicolas Gower, Alexandre Willaume, Chloé Antier, Loïc Renaud, Emilie Lévêque, Pierre Decazes, Stéphanie Becker, David Tonnelet, Philippe Gaulard, Hervé Tilly, Thierry Jo Molina, Alexandra Traverse-Glehen, Marie Donzel, Philippe Ruminy, and Fabrice Jardin
Subjects: Specialties of internal medicine, RC581-951
Abstract: Abstract: There is a scarcity of data on the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5ʹ rapid amplification of complimentary DNA ends (5′RACE) to tumor RNA samples from 137 patients with PMBL with available gene expression profiling and next-generation sequencing data. We obtained 5′RACE results for 75 of the 137 (54.7%) patients with the following clinical characteristics: median age (range), 33 years (18-64); female, 53.3%; performance status score 0 to 1, 86.7%; stage I to II, 57.3%; first-line treatment with anti-CD20 plus doxorubicin-based chemotherapy, 100%. Among the 60 biopsies that expressed a productive BCR, we highlighted a strong somatic hypermutation profile, defined as 81.1% and >78.6% of all complementarity-determining region 3 sequences for IgVH and IgVL, respectively. When compared with other patients, this subgroup had similar clinical characteristics but a greater median allele frequency for all somatic variants, a decreased BCR diversity, and greater expression of PDL1/PDL2 and MS4A1 genes, suggesting greater tumoral infiltration. We confirmed this poorer prognosis in a multivariate model and in an independent validation cohort in which 6 of 37 (16%) PMBL patients exhibited HCD (PFS: HR, 12; OS: HR, 17).
Published: 2025
Full Text: View/download PDF

2. Four Cases of Myeloproliferative Disorders Associated With Down Syndrome: Distinguishing ML-DS From TAM-DS

Author: Kévin Boumeghar, Sylvie Daliphard, Nimrod Buchbinder, Catherine Boutet, Dominique Penther, Pascaline Etancelin, Julien Bourgain, Gérard Buchonnet, Elsa Bera, and Victor Bobée
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Down syndrome (DS) is defined by an extra copy of chromosome 21 and confers an increased susceptibility to hematological disorders. Transient abnormal myelopoiesis (TAM) and myeloid-leukemia associated with Down syndrome (ML-DS) are two conditions that need to be accurately diagnosed to provide appropriate management. Both TAM and ML-DS are characterized by proliferation of megakaryoblasts carrying a mutation in the GATA1 gene. Here, we report four cases with educational significance, highlighting typical diagnostic features that facilitate the differentiation between these two conditions, thereby assisting clinicians and medical laboratory professionals in effectively managing and monitoring these patients.
Published: 2024
Full Text: View/download PDF

3. Complete hematologic response after belinostat treatment and allogeneic stem cell transplantation for multiple relapsed/refractory angioimmunoblastic T‐cell lymphoma: A case report

Author: Vincent Camus, Pascaline Etancelin, Fanny Drieux, Elena‐Liana Veresezan, Jean‐Michel Picquenot, Dominique Penther, Mathieu Viennot, Philippe Ruminy, Nathalie Contentin, Emilie Lemasle, Stéphane Leprêtre, Sydney Dubois, Juliette Penichoux, Aspasia Stamatoullas, Alexandra Zduniak, Hélène Lanic, and Fabrice Jardin
Subjects: allogenic stem cell transplantation, belinostat, complete response, HDAC inhibitor, nTFHL‐AI, PTCL, Medicine, Medicine (General), R5-920
Abstract: Key Clinical Message This case report highlights the potential of belinostat for the treatment of relapsed/refractory peripheral T‐cell lymphomas, for which effective therapies are still scarce. Abstract Peripheral T‐cell lymphomas have an aggressive disease course associated with poor outcomes. We report a young patient with highly pretreated relapsed/refractory nodal follicular helper T‐cell lymphoma (angioimmunoblastic‐type [nTFHL‐AI]), who successfully received an allogeneic stem cell transplantation following belinostat therapy. The complete hematologic response achieved has lasted more than 2 years.
Published: 2023
Full Text: View/download PDF

4. Successful treatment of T/myeloid mixed‐phenotype acute leukemia with the translocation (10;11)(p13;q14) PICALM/AF10 with 3 + 7 myeloid standard treatment: A case report

Author: Daphné Krzisch, Alexandra Zduniak, Elena‐Liana Veresezan, Sylvie Daliphard, Nathalie Contentin, Dominique Penther, Pascaline Etancelin, Fabrice Jardin, and Vincent Camus
Subjects: mixed‐phenotype acute leukemia, PICALM‐AF10, translocation (1011)(p13q14), Medicine, Medicine (General), R5-920
Abstract: Abstract The translocation PICALM/AF10 is described in multilineage diseases. We report a patient with PICALM/AF10 T/myeloid mixed‐phenotype acute leukemia who achieved durable complete remission after AML‐like treatment suggesting a myeloid origin.
Published: 2021
Full Text: View/download PDF

5. Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers

Author: Pierre-Julien Viailly, Vincent Sater, Mathieu Viennot, Elodie Bohers, Nicolas Vergne, Caroline Berard, Hélène Dauchel, Thierry Lecroq, Alison Celebi, Philippe Ruminy, Vinciane Marchand, Marie-Delphine Lanic, Sydney Dubois, Dominique Penther, Hervé Tilly, Sylvain Mareschal, and Fabrice Jardin
Subjects: UMI, CNV calling, Next generation sequencing, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract: Abstract Background Recently, copy number variations (CNV) impacting genes involved in oncogenic pathways have attracted an increasing attention to manage disease susceptibility. CNV is one of the most important somatic aberrations in the genome of tumor cells. Oncogene activation and tumor suppressor gene inactivation are often attributed to copy number gain/amplification or deletion, respectively, in many cancer types and stages. Recent advances in next generation sequencing protocols allow for the addition of unique molecular identifiers (UMI) to each read. Each targeted DNA fragment is labeled with a unique random nucleotide sequence added to sequencing primers. UMI are especially useful for CNV detection by making each DNA molecule in a population of reads distinct. Results Here, we present molecular Copy Number Alteration (mCNA), a new methodology allowing the detection of copy number changes using UMI. The algorithm is composed of four main steps: the construction of UMI count matrices, the use of control samples to construct a pseudo-reference, the computation of log-ratios, the segmentation and finally the statistical inference of abnormal segmented breaks. We demonstrate the success of mCNA on a dataset of patients suffering from Diffuse Large B-cell Lymphoma and we highlight that mCNA results have a strong correlation with comparative genomic hybridization. Conclusion We provide mCNA, a new approach for CNV detection, freely available at https://gitlab.com/pierrejulien.viailly/mcna/ under MIT license. mCNA can significantly improve detection accuracy of CNV changes by using UMI.
Published: 2021
Full Text: View/download PDF

6. Light chain lambda myeloma with fatal AL cardiac amyloidosis in a 21‐year‐old patient: A case report and review

Author: Vincent Camus, Sydney Dubois, Pierre‐Alain Thiébaut, Stéphane Lepretre, Pascal Lenain, Jean‐Michel Picquenot, Elena‐Liana Veresezan, Arnaud François, Dominique Penther, Fabrice Bauer, Arnaud Jaccard, and Fabrice Jardin
Subjects: cardiac involvement, chemotherapy, daratumumab, light chain myeloma, multi‐organ amyloidosis, Medicine, Medicine (General), R5-920
Abstract: Abstract Multi‐organ AL amyloidosis is a therapeutic challenge because of light chain deposits severely damaging the function of concerned organs. Cardiac involvement, which leads to concentric hypertrophy of both ventricles, is particularly severe and leads to poor prognosis regardless of combination chemotherapy. This case pinpoints the relevance of combining clinical, histological, and echocardiographic information in the management of this complex and life‐threatening disease.
Published: 2019
Full Text: View/download PDF

7. Concomitant occurrence of genetically distinct Hodgkin lymphoma and primary mediastinal lymphoma

Author: Sydney Dubois, Philippe Ruminy, Elodie Bohers, Pierre‐Julien Viailly, Liana Veresezan, Jean‐Michel Picquenot, Victor Bobée, Mathieu Viennot, Dominique Penther, Vincent Camus, Catherine Thieblemont, Camille Pouaty, Hervé Tilly, and Fabrice Jardin
Subjects: Hodgkin lymphoma, molecular characterization, primary mediastinal lymphoma, Medicine, Medicine (General), R5-920
Abstract: Abstract Synchronous Hodgkin Lymphoma and Primary Mediastinal B‐cell Lymphoma is possible, with molecular analyses proving the absence of clonal filiation between both entities. This suggests a common etiology but the existence of two divergent clones.
Published: 2021
Full Text: View/download PDF

8. B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL

Author: Benjamin Fournier, Estelle Balducci, Nicolas Duployez, Emmanuelle Clappier, Wendy Cuccuini, Chloé Arfeuille, Aurélie Caye-Eude, Eric Delabesse, Elodie Bottollier-Lemallaz Colomb, Karin Nebral, Marie-Lorraine Chrétien, Coralie Derrieux, Aurélie Cabannes-Hamy, Florent Dumezy, Pascaline Etancelin, Odile Fenneteau, Jamile Frayfer, Antoine Gourmel, Marie Loosveld, Gérard Michel, Nathalie Nadal, Dominique Penther, Isabelle Tigaud, Elise Fournier, Bettina Reismüller, Andishe Attarbaschi, Marina Lafage-Pochitaloff, and André Baruchel
Subjects: acute lymphoblastic leukemia, cytogenetics and molecular genetics, clinical and molecular epidemiology, eosinophilia, IKZF1 rearrangement, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: B-cell acute lymphoblastic leukemia associated with t(5;14)(q31;q32); IGH-IL3 is an exceptional cause of eosinophilia. The IGH enhancer on 14q32 is juxtaposed to the IL3 gene on 5q31, leading to interleukin-3 overproduction and release of mature eosinophils in the blood. Clinical, biological and outcome data are extremely scarce in the literature. Except for eosinophilia, no relevant common feature has been highlighted in these patients. However, it has been classified as a distinct entity in the World Health Organization classification.Cases Presentation: Eight patients with t(5;14)(q31;q32) treated by French or Austrian protocols were retrospectively enrolled. Array comparative genomic hybridization, multiplex ligation-dependent probe amplification or genomic PCR search for IKZF1 deletion were performed in 7. Sixteen patients found through an exhaustive search in the literature were also analyzed.For those 24 patients, median age at diagnosis is 14.3 years with a male predominance (male to female ratio = 5). Eosinophilia-related symptoms are common (neurologic in 26%, thromboembolic in 26% or pulmonary in 50%). Median white blood cells count is high (72 × 109/L) and linked to eosinophilia (median: 32 × 109/L). Peripheral blasts are present at a low level or absent (median: 0 × 109/L; range: 0–37 × 109/L). Bone marrow morphology is marked by a low blast infiltration (median: 42%). We found an IKZF1 deletion in 5 out of 7 analyzable patients Outcome data are available for 14 patients (median follow-up: 28 months): 8 died and 6 are alive in complete remission.Some of these features are concordant with those seen in patients with other IGH-rearranged B-cell acute lymphoblastic leukemias: young age at onset, male sex, low blast count, high incidence of IKZF1 deletion and intermediate prognosis.Conclusion: Based on shared epidemiological and biological features, B-cell acute lymphoblastic leukemia with t(5;14)(q31;q32) is a peculiar subset of IGH-rearranged B-cell acute lymphoblastic leukemia with an intermediate prognosis and particular clinical features related to eosinophilia.
Published: 2019
Full Text: View/download PDF

9. Poor prognosis of chromosome 7 clonal aberrations in Philadelphia-negative metaphases and relevance of potential underlying myelodysplastic features in chronic myeloid leukemia

Author: Audrey Bidet, Stéphanie Dulucq, Thomas Smol, Alice Marceau-Renaut, Stéphane Morisset, Valérie Coiteux, Marie-Pierre Noël-Walter, Franck-Emmanuel Nicolini, Isabelle Tigaud, Isabelle Luquet, Stéphanie Struski, Baptiste Gaillard, Dominique Penther, Sylvie Tondeur, Nathalie Nadal, Eric Hermet, Lauren Véronèse, Delphine Réa, Carine Gervais, Olivier Theisen, Christine Terré, Pascale Cony-Makhoul, Christine Lefebvre, Jean-Baptiste Gaillard, Isabelle Radford, Anne-Laure Vervaeke, Carole Barin, Elise Chapiro, Florence Nguyen-Khac, Gabriel Etienne, Claude Preudhomme, François Xavier Mahon, and Catherine Roche-Lestienne
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Clonal chromosome abnormalities in Philadelphia-negative cells could concern chronic myeloid leukemia patients treated by tyrosine kinase inhibitors. The European LeukemiaNet distinguishes -7/del(7q) abnormalities as a “warning”. However, the impact of clonal chromosome abnormalities, and specifically those of -7/del(7q), in Philadelphia-negative cells on clinical outcomes is unclear and based on case-reports showing morphological dysplasia and increased risk of acute myeloid leukemia, suggesting the coexistence of chronic myeloid leukemia and high-risk myelodysplastic syndrome. The aim of this study was to determine whether the impact of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells on the clinical outcome is different from that of other types of abnormalities, and we argue for an underlying associated high-risk myelodysplastic syndrome. Among 102 chronic myeloid leukemia patients with clonal chromosome abnormalities in Philadelphia-negative cells with more than a median of 6 years of follow up, patients with -7/del(7q) more frequently had signs of dysplasia, a lower cumulative incidence of deep molecular response and often needed further treatment lines, with the consequent impact on event-free and progression-free survival. Morphological features of dysplasia are associated with myelodysplastic syndrome/acute myeloid leukemia mutations and compromise the optimal response to tyrosine kinase inhibitors, irrespectively of the type of clonal chromosome abnormalities in Philadelphia-negative cells. However, mutation patterns determined by next-generation sequencing could not clearly explain the underlying high-risk disease. We hereby confirm the pejorative prognostic value of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells and suggest that myelodysplastic features constitute a warning signal that response to tyrosine kinase inhibitors may be less than optimal.
Published: 2019
Full Text: View/download PDF

10. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

Author: Florence Nguyen-Khac, Jerome Lambert, Elise Chapiro, Aurore Grelier, Sarah Mould, Carole Barin, Agnes Daudignon, Nathalie Gachard, Stéphanie Struski, Catherine Henry, Dominique Penther, Hossein Mossafa, Joris Andrieux, Virginie Eclache, Chrystèle Bilhou-Nabera, Isabelle Luquet, Christine Terre, Laurence Baranger, Francine Mugneret, Jean Chiesa, Marie-Joelle Mozziconacci, Evelyne Callet-Bauchu, Lauren Veronese, Hélène Blons, Roger Owen, Julie Lejeune, Sylvie Chevret, Hélène Merle-Beral, and Véronique Leblond
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (
Published: 2013
Full Text: View/download PDF

11. Multicenter study of ZAP-70 expression in patients with B-cell chronic lymphocytic leukemia using an optimized flow cytometry method

Author: Nathalie Gachard, Aurélie Salviat, Catherine Boutet, Christine Arnoulet, Françoise Durrieu, Bernard Lenormand, Stéphane Leprêtre, Sylviane Olschwang, Fabrice Jardin, Marina Lafage-Pochitaloff, Dominique Penther, Danielle Sainty, Liliane Reminieras, Jean Feuillard, and Marie C. Béné
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background Flow cytometry allows specific assessment of the expression of ZAP-70, a promising new prognostic factor in B-cell chronic lymphocytic leukemia (B-CLL), but suffers from a lack of multicenter standardization.Design and Methods An optimized method for direct detection of ZAP-70 in flow cytometry was tested in a multicenter fashion. Adapted for frozen cells, this method includes a normalization step by addition of B cells from a pool of peripheral blood mononuclear cells collected from normal donors. ZAP-70 expression levels were assessed for 153 patients with typical B-cell chronic lymphocytic leukemia chronic lymphocytic leukemia. Results were expressed as the ratio of ZAP-70 mean fluorescence intensity between B-CLL cells and normal B cells.Results The statistically optimized cut-off of ZAP-70 positivity was a ratio of 1.4. Concordance between ZAP-70 and CD38 expression was 67%. Concordance between the mutational status of IgVH genes and ZAP-70 or CD38 expression was 87% and 65%, respectively. ZAP-70 was significantly expressed in 28%, 54% and 61% of patients with Binet stages A, B and C B-cell chronic lymphocytic leukemia, respectively (p=0.008). The absence of ZAP-70 expression was associated with isolated del(13q14), a cytogenetic abnormality with a good prognosis, while most patients with the del(17p13) poor prognosis cytogenetic marker expressed ZAP-70 (p
Published: 2008
Full Text: View/download PDF

12. Application of the cghRA framework to the genomic characterization of Diffuse Large B-Cell Lymphoma.

Author: Sylvain Mareschal, Philippe Ruminy, Marion Alcantara, Céline Villenet, Martin Figeac, Sydney Dubois, Philippe Bertrand, Abdelilah Bouzelfen, Pierre-Julien Viailly, Dominique Penther, Hervé Tilly, Christian Bastard, and Fabrice Jardin
Published: 2017
Full Text: View/download PDF

13. Table S5. Cohort variants. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: This table presents all variants identified among our cohort by Lymphopanel NGS. Variant type and variant allele frequency (VAF) are indicated.
Published: 2023
Full Text: View/download PDF

14. Table S6. Cohort copy number variations. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: This table presents all CNVs identified among our cohort using the ONCOCNV software. Duplication was considered when copy number was superior to 2 and deletion was considered when copy number was inferior to 2. False discovery rate (FDR) cutoff was set at 0.01.
Published: 2023
Full Text: View/download PDF

15. Supplementary Figures from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Supplementary Figures 1-10 Figure S1. MYD88 mutation VAF according to L265P or non-L265P variants. Figure S2. Age according to MYD88 mutation status and variant among ABC patients. Figure S3. Genomic profiles of DLBCL according to the presence of MYD88 L265P or non-L265P variants. Figure S4. Relative L265P allele expression level according to L265P VAF. Figure S5. Gene expression according to MYD88 status. Figure S6. NFkB pathway gene expression according to MYD88 mutational status. Figure S7. LPS score according to subtype and downstream NFkB alterations. Figure S8. Clustering according to expression levels of 27 genes involved in LPS response and differentially expressed according to MYD88 L265P. Figure S9. TNFAIP3 and CARD11 expression according to their copy number status. Figure S10. Additional survival analyses.
Published: 2023
Full Text: View/download PDF

16. Table S10. Clinical characteristics of patients with CNS relapse. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Clinical characteristics of the 17 patients with CNS relapse are provided, included time to CNS relapse, first-line treatment and response after first-line treatment. CR, Complete Response; PR, Partial Response; PD, Progressive Disease.
Published: 2023
Full Text: View/download PDF

17. Table S1. Clinical and immunohistochemical data according to MYD88 mutation status. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: All relevant clinical data is included. Immunohistochemical results for BCL2, CD10, BCL6, MUM1, FOXP1, IgM and MYC are transcribed: 0 indicates negativity and 1 indicates positivity. For BCL2 and MYC, positivity is according to a threshold of 50% or 40% respectively.
Published: 2023
Full Text: View/download PDF

18. Data from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Purpose: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL), leading to constitutive NFκB pathway activation. The aim of this study was to examine the distinct genomic profiles of MYD88-mutant DLBCL, notably according to the presence of the L265P or other non-L265P MYD88 variants.Experimental Design: A cohort of 361 DLBCL cases (94 MYD88 mutant and 267 MYD88 wild-type) was submitted to next-generation sequencing (NGS) focusing on 34 genes to analyze associated mutations and copy number variations, as well as gene expression profiling, and clinical and prognostic analyses.Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P–mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis also segregated subgroups according to associated genetic alterations among patients with the same MYD88 mutation. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFκB pathway activation, although the majority of MYD88 L265P–mutant cases harbors downstream NFκB alterations, which can predict BTK inhibitor resistance. Finally, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P–mutant ABC DLBCL in our cohort.Conclusions: This study highlights the relative heterogeneity of MYD88-mutant DLBCL, adding to the field's knowledge of the theranostic importance of MYD88 mutations, but also of associated alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. Clin Cancer Res; 23(9); 2232–44. ©2016 AACR.
Published: 2023
Full Text: View/download PDF

19. Supplementary Data from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Supplementary methods, supplementary figure & table legends, and supplementary tables 3, 4, 8 & 9. Table S3: Overview of the Lymphopanel used for NGS analysis. Table S4: Overview of pathway selection Table S8. Genes involved in the LPS score. Table S9. Expression levels of genes involved in response to LPS stimulation according to MYD88 L265P.
Published: 2023
Full Text: View/download PDF

20. Table S7. Immunohistochemical markers and gene rearrangements according to MYD88 variants. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: Statistically significant differences (p
Published: 2023
Full Text: View/download PDF

21. Table S2. Cell of origin according to MYD88 mutations. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
Abstract: COO information according to the three techniques used in this study is given according to the various MYD88 variants present in our cohort.
Published: 2023
Full Text: View/download PDF

22. Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes

Author: François Lifermann, Jean-Alain Martignoles, Anne Quinquenel, Vincent Parinet, Christine Lefebvre, Pierre Hirsch, Mélanie Martin, Sabine Defasque, Florence Nguyen-Khac, Matthieu Decamp, Laurence Simon, Dominique Penther, Nadia Ali-Ammar, Elise Chapiro, Odile Maarek, Chrystele Bilhou-Nabera, Baptiste Gaillard, Agathe Maillon, Jean-Baptiste Micol, Marine Baron, Nathalie Auger, Stéphanie Struski, Damien Roos-Weil, Sylvie Tondeur, Marie-Joelle Mozziconacci, Audrey Bidet, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Robert Debré, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire CERBA [Saint Ouen l'Aumône], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier de Dax, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HAL-SU, Gestionnaire, École Pratique des Hautes Études (EPHE), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Oncology, Myeloid, [SDV]Life Sciences [q-bio], Chromosomal translocation, Translocation, Genetic, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, 12), In Situ Hybridization, Fluorescence, Aged, 80 and over, CHIC2, Middle Aged, Immunohistochemistry, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, medicine.anatomical_structure, RUNX1, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Cohort, Molecular Medicine, Female, Original Article, Chromosomes, Human, Pair 4, medicine.medical_specialty, IDH1, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, acute myeloid leukaemia, Genetic Association Studies, Aged, Chromosome Aberrations, Chromosomes, Human, Pair 12, Myeloproliferative Disorders, business.industry, Myelodysplastic syndromes, Original Articles, ETV6, Cell Biology, medicine.disease, myelodysplastic syndrome, t(4, chemistry, Fusion transcript, Myelodysplastic Syndromes, prognosis, business, 030215 immunology
Abstract: International audience; Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.
Published: 2021
Full Text: View/download PDF

23. Optical genome mapping, a promising alternative to gold standard cytogenetic approaches in a series of acute lymphoblastic leukemias

Author: Jean-Pierre Marolleau, Guillaume Jedraszak, Catherine Devoldere, Nicolas Duployez, Isabelle Luquet, Michaela West, Dominique Penther, Claude Preudhomme, Hakim Ouled-Haddou, Valentin Lestringant, Coralie Derrieux, Anne Lutun, Yann Ferret, Loïc Garçon, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie [CHU Amiens], Service Hydrographique et Océanographique de la Marine (SHOM), Ministère de la Défense, and Université de Picardie Jules Verne (UPJV)
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, [SDV]Life Sciences [q-bio], Computational biology, Biology, Polymorphism, Single Nucleotide, Translocation, Genetic, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gene mapping, Biomarkers, Tumor, Genetics, medicine, Humans, Multiplex, Child, Cytogenetics, Chromosome Mapping, Karyotype, Variant allele, Gold standard (test), Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Gene Expression Regulation, Neoplastic, Child, Preschool, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Acute lymphoblastic leukemias, Female, Cytogenetic Techniques
Abstract: International audience; Acute lymphoblastic leukemias (ALL) are characterized by a large number of cytogenetic abnormalities of clinical interest that require the use of several complementary techniques. Optical genome mapping (OGM) is based on analysis of ultra-high molecular weight DNA molecules that provides a high-resolution genome-wide analysis highlighting copy number and structural anomalies, including balanced translocations. We compared OGM to standard techniques (karyotyping, fluorescent in situ hybridization, single nucleotide polymorphism-array and reverse transcription multiplex ligation-dependent probe amplification) in 10 selected B or T-ALL. Eighty abnormalities were found using standard techniques of which 72 (90%) were correctly detected using OGM. Eight discrepancies were identified, while 12 additional anomalies were found by OGM. Among the discrepancies, four were detected in raw data but not retained because of filtering issues. However, four were truly missed, either because of a low variant allele frequency or because of a low coverage of some regions. Of the additional anomalies revealed by OGM, seven were confirmed by another technique, some of which are recurrent in ALL such as LMO2-TRA and MYC-TRB fusions. Despite false positive anomalies due to background noise and a case of inter-sample contamination secondarily identified, the OGM technology was relatively simple to use with little practice. Thus, OGM represents a promising alternative to cytogenetic techniques currently performed for ALL characterization. It enables a time and cost effective analysis allowing identification of complex cytogenetic events, including those currently inaccessible to standard techniques.
Published: 2021
Full Text: View/download PDF

24. Prognostic relevance of lymphocyte-to-monocyte ratio in primary myelodysplastic syndromes: a single center experience

Author: Sylvie Daliphard, Aspasia Stamatoullas, Juliette Pénichoux, Gérard Buchonnet, Hervé Tilly, Vincent Camus, Daphné Krzisch, Emilie Lemasle, Sydney Dubois, Fabrice Jardin, Dominique Penther, Christian Bastard, Anne-Lise Menard, Hélène Lanic, Nathalie Contentin, Pascal Lenain, and Stéphane Leprêtre
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Lymphocyte, Disease, Single Center, Monocytes, 03 medical and health sciences, 0302 clinical medicine, Text mining, hemic and lymphatic diseases, Internal medicine, Humans, Medicine, Lymphocytes, Retrospective Studies, Acute leukemia, business.industry, Myelodysplastic syndromes, Monocyte, Hematology, Prognosis, medicine.disease, medicine.anatomical_structure, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract: In myelodysplastic syndromes (MDS), the prognosis of the disease is related partly to the complications of blood cytopenias, and partly to the risk of transformation, over time, into acute leukemia...
Published: 2021
Full Text: View/download PDF

25. The 5th edition of the WHO classification of haematolymphoid tumors: comments from the Groupe Francophone de Cytogénétique Hématologique (GFCH)

Author: Florence Nguyen-Khac, Audrey Bidet, Marie-Bérengère Troadec, Lauren Veronese, Nathalie Auger, Agnes Daudignon, Nathalie Nadal, Dominique Penther, Lucienne Michaux, Marina Lafage-Pochitaloff, and Christine Lefebvre
Subjects: Cancer Research, Oncology, Hematology
Published: 2023
Full Text: View/download PDF

26. Successful treatment of T/myeloid mixed‐phenotype acute leukemia with the translocation (10;11)(p13;q14) PICALM/AF10 with 3 + 7 myeloid standard treatment: A case report

Author: Sylvie Daliphard, Vincent Camus, Pascaline Etancelin, Elena-Liana Veresezan, Fabrice Jardin, Dominique Penther, Nathalie Contentin, Alexandra Zduniak, and Daphné Krzisch
Subjects: Myeloid, lcsh:Medicine, Chromosomal translocation, Case Report, Case Reports, 030204 cardiovascular system & hematology, PICALM, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, translocation (1011)(p13q14), medicine, mixed‐phenotype acute leukemia, Acute leukemia, lcsh:R5-920, Mixed phenotype acute leukemia, business.industry, Standard treatment, lcsh:R, Complete remission, General Medicine, PICALM‐AF10, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, business, lcsh:Medicine (General)
Abstract: The translocation PICALM/AF10 is described in multilineage diseases. We report a patient with PICALM/AF10 T/myeloid mixed‐phenotype acute leukemia who achieved durable complete remission after AML‐like treatment suggesting a myeloid origin.
Published: 2021

27. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11

Author: Virginie Eclache, John Boudjarane, Naïs Prade, Stéphanie Struski, Laetitia Largeaud, Cyril Broccardo, Joop H. Jansen, Christine Terré, Marie-Agnès Collonge-Rame, Pierre-Yves Juvin, Dominique Penther, Stéphanie Lagarde, Antoine Ittel, Véronique Mansat-De Mas, G Ameye, Isabelle Luquet, Marina Lafage-Pochitaloff, Carole Barin, David Rombaut, Bastien Gerby, Carine Gervais, Steven Richebourg, Oliver M. Dovey, Pierre Bories, Christine Lefebvre, Isabelle Radford-Weiss, Audrey Bidet, Isabelle Tigaud, George S. Vassiliou, Benedicte Ribourtout, Tobias Tekath, Michaela Fontenay, Lucienne Michaux, Sylvie Hébrard, Hélène Antoine-Poirel, Laura Jamrog, Vincent Fregona, Nathalie Nadal, Eric Delabesse, Véronique Baccini, Kosuke Yusa, Gerby, Bastien [0000-0002-2657-4200], Baccini, Véronique [0000-0003-3913-7664], Largeaud, Laetitia [0000-0001-5341-5427], Fregona, Vincent [0000-0003-4857-1737], Prade, Naïs [0000-0003-4718-7848], Jamrog, Laura [0000-0003-2288-0806], Mansat-De Mas, Véronique [0000-0003-1878-9129], Dovey, Oliver M [0000-0003-3586-4813], Yusa, Kosuke [0000-0002-3442-021X], Vassiliou, George S [0000-0003-4337-8022], Jansen, Joop H [0000-0001-9459-568X], Tekath, Tobias [0000-0002-9315-5452], Rombaut, David [0000-0001-8910-0945], Ameye, Geneviève [0000-0002-5838-2879], Ittel, Antoine [0000-0001-5067-575X], Michaux, Lucienne [0000-0002-8357-7942], Poirel, Hélène A [0000-0002-0712-5127], Struski, Stéphanie [0000-0002-2282-4364], Fontenay, Michaela [0000-0002-5492-6349], Broccardo, Cyril [0000-0003-3016-6549], Delabesse, Eric [0000-0002-0928-0753], Apollo - University of Cambridge Repository, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: INVOLVEMENT, Candidate gene, Myeloid, Tumor suppressor gene, SCORING SYSTEM, [SDV]Life Sciences [q-bio], Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Biology, CLASSIFICATION, 03 medical and health sciences, Mice, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Animals, Humans, Genes, Tumor Suppressor, TSLC1/IGSF4, 030304 developmental biology, MYELODYSPLASTIC SYNDROME, 0303 health sciences, Science & Technology, Myeloid Neoplasia, Myelodysplastic syndromes, MALE-INFERTILITY, Chromosomes, Human, Pair 11, TSLC1, Cell Adhesion Molecule-1, Myeloid leukemia, KARYOTYPE, Hematology, medicine.disease, 3. Good health, Transplantation, Leukemia, Myeloid, Acute, medicine.anatomical_structure, KMT2A, 030220 oncology & carcinogenesis, CELL-ADHESION MOLECULE, Myelodysplastic Syndromes, Cancer research, biology.protein, Female, Bone marrow, Chromosome Deletion, Life Sciences & Biomedicine, LEUKEMIA
Abstract: Key Points We detail at clinical, cytological, cytogenetic, and molecular levels 113 cases of MDS and MDS/MPN with del(11q), a rare recurrent event.CADM1, a tumor suppressor gene identified initially in solid tumors, ATM, CBL, and KMT2A are deleted and/or mutated in del(11q)., Visual Abstract, Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.
Published: 2022
Full Text: View/download PDF

28. Concomitant occurrence of genetically distinct Hodgkin lymphoma and primary mediastinal lymphoma

Author: Catherine Thieblemont, Liana Veresezan, Hervé Tilly, Fabrice Jardin, Vincent Camus, Elodie Bohers, Dominique Penther, Pierre-Julien Viailly, Victor Bobée, Mathieu Viennot, Sydney Dubois, Philippe Ruminy, Camille Pouaty, Jean-Michel Picquenot, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Bohers, Elodie
Subjects: Pathology, medicine.medical_specialty, primary mediastinal lymphoma, business.industry, [SDV]Life Sciences [q-bio], Case Report, General Medicine, medicine.disease, Lymphoma, [SDV] Life Sciences [q-bio], molecular characterization, Primary Mediastinal Lymphoma, immune system diseases, Concomitant, hemic and lymphatic diseases, Etiology, Medicine, Hodgkin lymphoma, business, ComputingMilieux_MISCELLANEOUS
Abstract: Synchronous Hodgkin Lymphoma and Primary Mediastinal B‐cell Lymphoma is possible, with molecular analyses proving the absence of clonal filiation between both entities. This suggests a common etiology but the existence of two divergent clones.
Published: 2021
Full Text: View/download PDF

29. Recommendations for cytogenomic analysis of hematologic malignancies: comments from the Francophone Group of Hematological Cytogenetics (GFCH)

Author: Florence Nguyen-Khac, Agnès Daudignon, Dominique Penther, Marie-Bérengère Troadec, Christine Lefebvre, Audrey Bidet, Marina Lafage-Pochitaloff, Lauren Veronese, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biologie des Tumeurs and Laboratoire d'Hématologie Biologique, Centre Hospitalo-Universitaire CHU Bordeaux, F-33000, Bordeaux., Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier de Valenciennes, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cancer Research, medicine.medical_specialty, Hematology, business.industry, [SDV]Life Sciences [q-bio], Cytogenetics, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematologic Neoplasms, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: International audience
Published: 2020
Full Text: View/download PDF

30. Optical Mapping, a Promising Alternative to Gold Standard Cytogenetic Approaches in Acute Lymphoblastic Leukemias: A Blind Comparison on 10 Patients

Author: Nicolas Duployez, Joyce S. Lee, Valentin Lestringant, Nathalie Grardel, Anne Lutun, Michaela West, Yann Ferret, Dominique Penther, Loïc Garçon, Jean-Pierre Marolleau, Claude Preudhomme, Université de Picardie Jules Verne (UPJV), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, CHU Amiens-Picardie, Bionano Genomics Inc, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie [CHU Amiens], Service Hydrographique et Océanographique de la Marine (SHOM), and Ministère de la Défense
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Pseudoautosomal region, Cytogenetics, Locus (genetics), Chromosomal translocation, Karyotype, Cell Biology, Hematology, Computational biology, Biology, medicine.disease, Biochemistry, Gene mapping, medicine, Copy-number variation, Trisomy, ComputingMilieux_MISCELLANEOUS
Abstract: Acute lymphoblastic leukemias (ALL) are characterized by a large number of genetic abnormalities of prognostic and theranostic interest. Their detection requires the use of several conventional and molecular cytogenetic techniques in order to establish the most exhaustive genetic profile: conventional karyotype, FISH, SNP-Array and RT-MLPA for detection of fusion transcripts. Optical genome mapping technique is based on analysis of ultra-high molecular weight DNA (UHMW: 150 kbp-2.5 Mbp). It allows an automatic, high resolution, genome-wide detection of structural anomalies, including balanced translocations and copy number anomalies, making this technology a promising tool in ALL. However, very few data are available in ALL so far. Our objective was to compare optical mapping (Bionano Genomics) to standard techniques performed routinely (combination of karyotype, FISH, SNP-array and RT-MLPA) in 10 selected B or T-ALL patients carrying at least one major genetic abnormality including t(10;14) TLX1-TRA, t(9;22) BCR-ABL1 (e1a2 and e14a2 transcripts), t(10;11) MLLT10-PICALM, t(11;19) KMT2A-MLLT1, typical hyperdiploid profile, iAMP21, SET-NUP214 fusion, various deletions involving CDKN2A/CDKN2B, IKZF1, PAX5, PTEN, ERG and FBXW7. Abnormalities on SNP-array were retained when allele fraction was > 10% and larger than 1Mbp or > 20 kbp and involving one of the 186 genes defined as potentially relevant in leukemogenesis. A total of 79 anomalies meeting these criteria in SNP-array, and/or found by other standard techniques were identified (45 deletions, 16 whole chromosome gains, 10 duplications or partial gains, and 8 translocations). Bone marrow DMSO pellets from the 10 patients, all treated at the CHU Amiens-Picardie, were used for this study. The UHMW DNA extraction technique provided molecules with an average N50 (≥ 150 kbp) of 286 kbp, and an average coverage of 339x. Direct imaging of the DNA molecules was performed on the Bionano Saphyr system and structural variants were automatically detected using the Rare Variant Pipeline. Abnormalities analysis was blindly performed by two independent operators on the Bionano Access software (v 1.5.2.), one cytogeneticist with no training in optical mapping (operator 1) and the other optical mapping technician without training in cytogenetics (operator 2). Among the 79 relevant anomalies, 72 (91.1%) were found by operator 1 and 71 (89.9%) by operator 2. All (8/8) translocations, 43/45 (95.6%) of deletions, 8/10 (80%) of gains were found by both operators whereas 13/16 (81.25%) and 12/16 (75%) of chromosomal gains were found by operator 1 and 2 respectively. Concerning the 8 discrepancies between optical mapping and standard techniques, 4 of them were filtering issues. Three were low allelic frequency large gains clearly visible in raw data but rejected by software's CNV filters, totally, or partially for a trisomy 3 that caused the discrepancy between the two observers. The fourth was a deletion of VPREB1 gene, erroneously eliminated by operators because included in recurrent deletion zones of IGL locus. The 4 others discrepancies were non detected anomalies. Two of them were copy number variations in Xp22.33 (pseudoautosomal region), a non-covered area with the optical mapping technology, one of which was a P2RY8-CRLF2 fusion. Another sub-clonal gain (trisomy 21) found by karyotype and FISH (quantified at 7% of all nuclei) but not by SNP-array, was missed, even in raw data. The last was a near-tetraploid subclone, found only on karyotype, that might be strictly tetraploid and by definition undetectable by quantitative techniques. Interestingly, new anomalies, not detected by standard techniques, were revealed, including a translocation t(11;14)(p13;q11.2) LMO2-TRA, a translocation with inversion t(7;8)(q34;q24.1) TRB-MYC and a translocation t(14;20)(q32.33;q13.13) IGH-CEBPB. At last, in 3 cases, unidentified complex rearrangements by cytogenetics could be resolved using optical mapping. Thus, optical mapping represents an innovative, time and cost effective alternative to the different cytogenetic techniques currently performed routinely for ALL genetic characterization. It enables identification of complex cytogenetic events, including those currently inaccessible to standard techniques such as chromotripsis or certain complex translocations. Disclosures Lee: Bionano Genomics, San Diego: Current Employment. Ferret:Bionano Genomics: Research Funding.
Published: 2020
Full Text: View/download PDF

31. Isolated isochromosomes i(X)(p10) and idic(X)(q13) are associated with myeloid malignancies and dysplastic features

Author: Isabelle Rafdord-Weiss, Dominique Penther, Carole Barin, Baptiste Gaillard, Benoit Quilichini, Catherine Roche-Lestienne, Pascaline Etancelin, Christine Lefebvre, Daniel Lusina, Gwenaël Nadeau, Francine Mugneret, Catherine Godon, Virginie Eclache, Florence Nguyen-Khac, Yann Ferret, M J Mozziconacci, Antoine Ittel, Nathalie Nadal, Audrey Bidet, Gwendoline Soler, Elise Chapiro, Groupe Francophone de Cytogénétique Hématologique, Agnès Daudignon, Steven Richebourg, Pierre-Julien Viailly, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie biologique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital de la Timone [CHU - APHM] (TIMONE), Thales Communications [Colombes], THALES, CHU Bretonneau, CHU Clermont-Ferrand, Centre Hospitalier de Valenciennes, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service d'hématologie biologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Service d'hématologie biologique [Nantes] (Cytologie Hématologique), Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôtel-Dieu de Nantes, Service de Cytogénétique, Centre hospitalier de Valence, Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cytogenetics [Québec, Canada], Centre Hospitalier Universitaire du Québec (CHUQ)-Hôpital du Saint-Sacrement [CHU Québec] (HSS), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Picardie Jules Verne (UPJV), and Hôpital Avicenne [AP-HP]
Subjects: Male, Myeloid, [SDV]Life Sciences [q-bio], Isochromosome, Dioxygenases, 03 medical and health sciences, 0302 clinical medicine, Age Distribution, Bone Marrow, Proto-Oncogene Proteins, medicine, Neoplasm, Humans, Sex Distribution, Gene, ComputingMilieux_MISCELLANEOUS, Aged, Chromosomes, Human, X, business.industry, Follow up studies, Neoplasms, Second Primary, Hematology, Middle Aged, medicine.disease, 3. Good health, Neoplasm Proteins, DNA-Binding Proteins, Isochromosomes, Leukemia, medicine.anatomical_structure, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Mutation (genetic algorithm), Mutation, Cancer research, Age distribution, Female, business, 030215 immunology, Follow-Up Studies, Genes, Neoplasm
Abstract: International audience
Published: 2019
Full Text: View/download PDF

32. Cytogenetic landscape in 1012 newly diagnosed chronic lymphocytic leukemia

Author: Benoît Quilichini, Thomas Smol, Charles Herbaux, Sabine Tricot, Jania Bakala, Soraya Moulessehoul, Amel Senouci, Agnès Daudignon, and Dominique Penther
Subjects: Adult, Male, Monosomy, Chronic lymphocytic leukemia, Chromosomal translocation, Newly diagnosed, Ataxia Telangiectasia Mutated Proteins, Biology, Translocation, Genetic, Complex Karyotype, medicine, Humans, In Situ Hybridization, Fluorescence, Aged, Aged, 80 and over, Potential impact, Interleukin, Karyotype, Hematology, General Medicine, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Chromosome Banding, Cancer research, Female, Tumor Suppressor Protein p53, Gene Deletion
Abstract: Background Chronic lymphocytic leukemia (CLL) stratification mainly relies on FISH markers according to Dohner's hierarchical model which includes high-risk FISH markers, intermediate FISH, or low-risk FISH. Recently, complex karyotype (CK) has been demonstrated as an independent negative prognostic factor in CLL. Methods A series of 1012 untreated CLL patients have been investigated with both FISH and chromosome banding analysis (CBA) on the same pellet obtained from interleukin IL-2-CPG DSP30 oligonucleotide-stimulated cultured cells. Results Combining both FISH and CBA has led to refine prognostic categories with identification of 30% of CK in low-risk and intermediate FISH group. This raises the issue of switching them to a high-risk group. While this series confirmed the significant association between CK and high-risk FISH (P = .003), 33% of CK present no ATM or TP53 deletion. Three groups characterized by significant association between FISH markers and CBA have emerged: CK with TP53 loss and monosomy 15; CK with ATM loss and 14q32 translocation; and CK without ATM or TP53 losses but trisomies 12, 18, and 19 or t(14;18)(q32;q21). Conclusion We have observed that in addition to FISH analysis, the CBA allows detection of many abnormalities with potential impact on patient follow-up and treatment, mainly CK.
Published: 2019

33. Light chain lambda myeloma with fatal AL cardiac amyloidosis in a 21‐year‐old patient: A case report and review

Author: Sydney Dubois, Elena-Liana Veresezan, Arnaud Jaccard, Fabrice Jardin, Vincent Camus, Arnaud François, Pascal Lenain, Dominique Penther, Fabrice Bauer, Pierre-Alain Thiebaut, Jean-Michel Picquenot, Stéphane Leprêtre, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de Pathologie [CHU Rouen], Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Département d'Oncologie Génétique [Rouen] (CLCC Henri Becquerel), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service de cardiologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, CNR de l'amylose AL et des autres maladies par dépôt d'immunoglobulines monoclonales [CHU Limoges], Hôpital Dupuytren [CHU Limoges], VILLIER, Venceslas, Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
Subjects: Pathology, medicine.medical_specialty, multi‐organ amyloidosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, Concentric hypertrophy, Case Report, Case Reports, Disease, 030204 cardiovascular system & hematology, Immunoglobulin light chain, chemotherapy, 03 medical and health sciences, 0302 clinical medicine, AL amyloidosis, medicine, cardiac involvement, lcsh:R5-920, Chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, lcsh:R, Daratumumab, Combination chemotherapy, General Medicine, medicine.disease, daratumumab, 3. Good health, [SDV] Life Sciences [q-bio], Cardiac amyloidosis, 030220 oncology & carcinogenesis, light chain myeloma, lcsh:Medicine (General), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Multi-organ AL amyloidosis is a therapeutic challenge because of light chain deposits severely damaging the function of concerned organs. Cardiac involvement, which leads to concentric hypertrophy of both ventricles, is particularly severe and leads to poor prognosis regardless of combination chemotherapy. This case pinpoints the relevance of combining clinical, histological, and echocardiographic information in the management of this complex and life-threatening disease.
Published: 2019
Full Text: View/download PDF

34. Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B-cell lymphomas

Author: Vinciane Marchand, Pierre-Julien Viailly, Fabrice Jardin, Pascaline Etancelin, Philippe Ruminy, Sydney Dubois, Sylvain Mareschal, Jean Feuillard, Christian Bastard, Jean-Michel Picquenot, Elodie Bohers, Dominique Penther, Philippe Bertrand, Catherine Maingonnat, David Rizzo, and Hervé Tilly
Subjects: 0301 basic medicine, medicine.medical_specialty, Cytogenetics, Hematology, Biology, medicine.disease, Somatic evolution in cancer, 3. Good health, Lymphoma, 03 medical and health sciences, Negative selection, 030104 developmental biology, medicine.anatomical_structure, Immunology, medicine, Cancer research, Immunoglobulin heavy chain, IGHV@, Diffuse large B-cell lymphoma, B cell
Abstract: Little is known on the phylogenetic relationship between diagnostic and relapse clones of diffuse large B-cell lymphoma (DLBCL). We applied high throughput sequencing (HTS) of the VDJ locus of Immunoglobulin heavy chain (IGHV) on 14 DLBCL patients with serial samples, including tumor biopsies and/or peripheral blood mononuclear cells (PBMC). Phylogenetic data were consolidated with targeted sequencing and cytogenetics. Phylogeny clearly showed that DLBCL relapse could occur according either an early or a late divergent mode. These two modes of divergence were independent from the elapsed time between diagnosis and relapse. We found no significant features for antigen selection pressure in complementary determining region both at diagnosis and relapse for 9/12 pairs and a conserved negative selection pressure for the three remaining cases. Targeted HTS and conventional cytogenetics revealed a branched vs. linear evolution for 5/5 IGHV early divergent cases, but unexpected such "oncogenetic" branched evolution could be found in at least 2/7 IGHV late divergent cases. Thus, if BCR signaling is mandatory for DLBCL emergence, oncogenetic events under chemotherapy selection pressure may be the main driving forces at relapse. Finally, circulating subclones with divergent IGHV somatic hypermutations patterns from initial biopsy could be detected in PBMC at diagnosis for 4/6 patients and, for two of them, at least one was similar to the ones found at relapse. This study highlights that oncogenetic intraclonal diversity of DLBCL should be evaluated beyond the scope a single biopsy and represents a rationale for future investigations using peripheral blood for lymphoid malignancies genotyping. Am. J. Hematol. 92:68-76, 2017. © 2016 Wiley Periodicals, Inc.
Published: 2016
Full Text: View/download PDF

35. Cytogenetic place in managing myelodysplastic syndromes: an update by the Groupe francophone de cytogénétique hématologique (GFCH)

Author: Isabelle Tigaud, Virginie Eclache, Christine Lefebvre, Sophie Raynaud, Marina Lafage-Pochitaloff, and Dominique Penther
Subjects: 0301 basic medicine, Somatic cell, In situ hybridization, Biology, DNA sequencing, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Gene, In Situ Hybridization, Fluorescence, Societies, Medical, Comparative Genomic Hybridization, Myelodysplastic syndromes, High-Throughput Nucleotide Sequencing, Karyotype, Hematology, General Medicine, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Cancer research, France, Bone marrow, Comparative genomic hybridization
Abstract: The myelodysplastic syndromes (MDS) are preleukemic diseases of elderly patients characterized by defective maturation of clonal hematopoietic progenitor cells resulting in peripheral blood cytopenias. Clonal chromosomal abnormalities are heterogeneous and can be detected in less than 50% of patients with de novo MDS and more frequently in secondary MDS (up to 80%). The karyotype plays an important role in the pathogenesis, diagnosis, and prognosis to evaluate the risk of leukemic transformation and, more recently, in treatment allocation. The gold standard for cytogenetic diagnosis in MDS is conventional chromosome banding analyses of bone marrow metaphases. The most frequent abnormalities are deletions and losses of chromosomes 5 (-5/5q-) and 7 (-7/7q-) and various isolated or combined abnormalities. Fluorescent in situ hybridization and array comparative genomic hybridization can reveal cryptic genetic abnormalities but are not recommended in routine diagnosis. New techniques including next generation sequencing revealed somatic driver mutations especially those affecting genes involved in RNA splicing or those harboring important prognostic value (TP53, ASXL1…) with potential applications in clinical practice in the future.
Published: 2016
Full Text: View/download PDF

36. Genetic differences between paediatric and adult Burkitt lymphomas

Author: Xavier Pepermans, Carole Barin, Hélène Poirel, Nicole Dastugue, Ivan Théate, Martine Raphael, Violaine Havelange, Geneviève Ameye, Lucienne Michaux, Evelyne Callet-Bauchu, Miikka Vikkula, Francine Mugneret, Dominique Penther, and Eric Lippert
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Loss of Heterozygosity, Loss of heterozygosity, 03 medical and health sciences, Exon, 0302 clinical medicine, CDKN2A, hemic and lymphatic diseases, Internal medicine, medicine, Chromosomes, Human, Humans, Copy-number variation, Child, B-cell lymphoma, Chromosome Aberrations, Hematology, business.industry, Age Factors, Infant, medicine.disease, Burkitt Lymphoma, Neoplasm Proteins, Lymphoma, 030104 developmental biology, Child, Preschool, 030220 oncology & carcinogenesis, Immunology, Female, business, SNP array
Abstract: Dysregulation of MYC is the genetic hallmark of Burkitt lymphoma (BL) but it is encountered in other aggressive mature B-cell lymphomas. MYC dysregulation needs other cooperating events for BL development. We aimed to characterize these events and assess the differences between adult and paediatric BLs that may explain the different outcomes in these two populations. We analysed patterns of genetic aberrations in a series of 24 BLs: 11 adults and 13 children. We looked for genomic imbalances (copy number variations), copy-neutral loss of heterozygosity (CN-LOH) and mutations in TP53, CDKN2A, ID3 (exon 1), TCF3 (exon17) and CCND3 (exon 6). Young patients displayed more frequent 13q31.3q32.1 amplification, 7q32q36 gain and 5q23.3 CN-LOH, while 17p13 and 18q21.3 CN-LOH were only detected in adult BLs. ID3 mutations were present in all adult samples, but only in 42% of childhood cases. CCND3 and ID3 double-hit mutations, as well as 18q21 CN-LOH, seemed to be associated with poorer outcome. For the first time, we report different genetic anomalies between adult and paediatric BLs, suggesting age-related heterogeneity in Burkitt lymphomagenesis. This may explain the poorer prognosis of adult BLs. Additional studies are needed to confirm these results in the setting of clinical trials.
Published: 2016
Full Text: View/download PDF

37. Transformation of an Unclassified Myeloproliferative Neoplasm with a RareBCR-JAK2Fusion Transcript Resulting from the Translocation (9;22)(p24;q11)

Author: C. Kuadjovi, Hervé Tilly, Nathalie Contentin, Dominique Penther, Françoise Parmentier, Fabrice Jardin, P. Etancelin, Ali N. Chamseddine, Pascal Lenain, Vincent Camus, and Christian Bastard
Subjects: Pathology, medicine.medical_specialty, Myeloid, Derivative chromosome, lcsh:RC633-647.5, business.industry, breakpoint cluster region, food and beverages, Case Report, Chromosomal translocation, lcsh:Diseases of the blood and blood-forming organs, General Medicine, medicine.disease, Fusion gene, Transplantation, medicine.anatomical_structure, Fusion transcript, hemic and lymphatic diseases, medicine, Cancer research, business, Myeloproliferative neoplasm
Abstract: BCR-ABL1negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates aBCR-JAK2fusion gene by fusing theBCRat intron 13 toJAK2at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT). To the best of our knowledge, this is the thirteenth case reported worldwide to describe aBCR-JAK2fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. RegardingBCR-ABL1 negativeMPN patients this case report provides strong support for a role ofJAK2activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated.
Published: 2015
Full Text: View/download PDF

38. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P-Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author: Thierry Jo Molina, Fabrice Jardin, Marc André, Richard Delarue, Sylvain Mareschal, Philippe Bertrand, Thierry Fest, Corinne Haioun, Pierre-Julien Viailly, Martin Figeac, Philippe Ruminy, Dominique Penther, Vinciane Marchand, Sydney Dubois, Frederic Peyrade, Jean-Michel Picquenot, Karen Leroy, Jean-Philippe Jais, Christiane Copie-Bergman, Bruno Tesson, Catherine Maingonnat, Bettina Fabiani, Elodie Bohers, Fabienne Desmots, Hervé Tilly, Nicolas Ketterer, Thierry Lamy, Pauline Peyrouze, Gilles Salles, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Res Ctr, Institut Curie, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille 2 - Faculté de Médecine, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Hôpital Pontchaillou, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie [Mondor], Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Cliniques Universitaires UCL Mont-Godinne, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Service d'informatique médicale et biostatistiques [CHU Necker], Institut Carnot Lymphome (CALYM), Faculté de Médecine Henri Warembourg - Université de Lille, Interactions cellulaires et moléculaires (ICM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et cancer (MiCa), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Pathologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ), HEMATOLOGIE, CRLCC Henri Becquerel, Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Dept Translat Res, Breast Canc Biol Grp, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Carnot CALYM [Pierre-Benite], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Université Côte d'Azur (UCA)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Oncology, 0301 basic medicine, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Bioinformatics, medicine.disease_cause, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Targeted therapy, 0302 clinical medicine, CDKN2A, hemic and lymphatic diseases, Copy-number variation, Aged, 80 and over, Genetics, 0303 health sciences, Mutation, NF-kappa B, High-Throughput Nucleotide Sequencing, hemic and immune systems, Genomics, Hematology, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, Signal Transduction, Adult, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Genetic Heterogeneity, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, 030304 developmental biology, Genome, Human, Genetic heterogeneity, Germinal center, Cancer, Cell Biology, CD79B, medicine.disease, Lymphoma, Gene expression profiling, 030104 developmental biology, Myeloid Differentiation Factor 88, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: Introduction: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of Activated B-Cell like (ABC) Diffuse Large B Cell Lymphoma (DLBCL), leading to constitutive NFkB pathway activation. The frequency of MYD88 mutations in DLBCL and other hematologic malignancies is well described; however, there has not yet been a large-scale study of a MYD88 mutated patient cohort with additional Next Generation Sequencing (NGS), copy number variation (CNV), and gene expression data, in order to thoroughly characterize the associated genomic profiles of these patients. The aims of our study were to compare the L265P and non-L265P mutations in terms of pathological and genetic features, to better detail the genomic background associated with MYD88 mutations in order to delineate patients potentially sensitive to targeted therapies, and to define the prognostic value of MYD88 mutations according to different genomic contexts. Methods: A cohort of 361 DLBCL patients (94 MYD88 mutant and 267 MYD88 wild-type) was selected among the prospective, multicenter and randomized LNH-03B and LNH09-7B (NCT01195714) LYSA trials, as well as among patients sequenced at our institution as part of routine procedure. Cell of origin (COO) classification was obtained with HGU133+2.0 Affymetrix GeneChip arrays for 214 patients, with RT-MLPA for 77 patients1 and with Hans immunohistochemistry (IHC) method for 49 patients. All cases were submitted to next generation sequencing (NGS) focusing on 34 genes (Lymphopanel2) in order to analyze associated mutations and copy number variations (CNVs), as well as IHC, FISH, and clinical and prognostic analyses. Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis segregated subgroups according to associated genetic alterations among patients with either MYD88 L265P or non-L265P mutations. As such, clustering separated MYD88 L265P mutated DLBCL with associated PIM1 (52%), CD79B (52%), KMT2D (42%), and PRDM1 (32%) mutations, as well as MYD88 L265P mutated DLBCL with CDKN2A/B (67%/50%), PRDM1 (57%) and TNFAIP3 (52%) CNVs. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFkB pathway activation, although the majority of ABC MYD88 L265P mutant cases harbor downstream NFkB alterations, which can potentially predict BTK inhibitor resistance. Of note, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P mutant ABC DLBCL in our cohort both in OS (p=0.02) and PFS (p=0.01), whereas the association of CARD11 or TNFAIP3 alterations did not impact survival. Interestingly, MYD88 mutant DLBCL cases were significantly more likely to experience central nervous system (CNS) relapse than MYD88 WT cases (p=0.02), as were MYD88 L265P mutant cases specifically (p=0.03). This result still tended toward statistical significance when considering only ABC patients (7 of 11 ABC CNS-relapsing cases were MYD88 mutant, p=0.1) but would have to be confirmed in a larger cohort. Conclusions: This study highlights the relative heterogeneity of MYD88 mutant DLBCBL, adding to the field's knowledge of the distinct genetic backgrounds of these subgroups. Our data highlights the theranostic and prognostic relevance of examining MYD88 and associated genomic alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. 1. Mareschal S, Ruminy P, Bagacean C, et al. Accurate Classification of Germinal Center B-Cell-Like/Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase-Multiplex Ligation-Dependent Probe Amplification Assay: A CALYM Study. The Journal of molecular diagnostics : JMD. 2015;17(3):273-283. 2. Dubois S, Viailly P-J, Mareschal S, et al. Next Generation Sequencing in Diffuse Large B Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016;22(12):2919-2928. Disclosures Salles: Novartis: Consultancy, Honoraria; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.
Published: 2017
Full Text: View/download PDF

39. Hypoalbuminemia and hypergammaglobulinemia are associated with an increased infection risk in patients with myeloid malignancies treated with azacitidine. A 3-year monocentric retrospective study

Author: Pascal Lenain, Stéphane Leprêtre, Marion David, Nathalie Contentin, Hélène Lanic, Dominique Penther, Christian Bastard, Fabrice Jardin, Sylvain Mareschal, Emilie Lemasle, Hervé Tilly, Imene Rezine, Sylvie Daliphard, Ophélie Cassuto, Anne Lise Menard, Aspasia Stamatoullas, Service d'hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Service d'Hématologie, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Département d'Oncologie Génétique [Rouen] (CLCC Henri Becquerel), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), and Normandie Université (NU)-Normandie Université (NU)
Subjects: Risk, Antimetabolites, Antineoplastic, Cancer Research, medicine.medical_specialty, Myeloid, [SDV]Life Sciences [q-bio], Azacitidine, Infections, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hypergammaglobulinemia, Internal medicine, Humans, Medicine, In patient, Hypoalbuminemia, Antibiotic prophylaxis, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Myelodysplastic syndromes, Retrospective cohort study, Hematology, Antibiotic Prophylaxis, medicine.disease, 3. Good health, Surgery, medicine.anatomical_structure, Oncology, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, business, 030215 immunology, medicine.drug
Abstract: International audience
Published: 2015
Full Text: View/download PDF

40. Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index

Author: Isabelle Radford, Hassan Farhat, Christian Bastard, Sylvie Chevret, Fabrice Jardin, Clémentine Sarkozy, Dominique Penther, Franck Morschhauser, Sophie Rigaudeau, Sylvain Pilorge, Didier Bouscary, Richard Delarue, Catherine Roche-Lestienne, Hervé Tilly, Philippe Rousselot, Sylvie Castaigne, Olivier Hermine, and Christine Terré
Subjects: Oncology, Cancer Research, medicine.medical_specialty, biology, Proportional hazards model, Retrospective cohort study, Blastoid, biology.organism_classification, medicine.disease, Lymphoma, International Prognostic Index, Internal medicine, Immunology, Complex Karyotype, Genetics, medicine, Mantle cell lymphoma, Survival rate
Abstract: Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis.
Published: 2013
Full Text: View/download PDF

41. Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature

Author: Nicole Dastugue, Carole Barin, Christian Bastard, Olivier A. Bernard, Lisa J. Russell, Stéphanie Struski, Dominique Penther, Nathalie Nadal, Peter Vandenberghe, Isabelle Tigaud, Christine Lefebvre, Elise Chapiro, Florence Nguyen-Khac, Francine Mugneret, Marie-Joelle Mozziconacci, Christine J. Harrison, Eric Lippert, Pascaline Talmant, Sylvie Taviaux, Isabelle Radford-Weiss, Serge Romana, and Hong-Anh Cung
Subjects: Adult, Male, Cancer Research, Adolescent, Chromosomal translocation, Biology, Molecular cloning, Real-Time Polymerase Chain Reaction, Translocation, Genetic, hemic and lymphatic diseases, Receptors, Erythropoietin, Genetics, medicine, Humans, Gene family, Cloning, Molecular, Child, Molecular Biology, Gene, In Situ Hybridization, Fluorescence, B cell, Aged, Aged, 80 and over, Chromosomes, Human, Pair 14, medicine.diagnostic_test, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Real-time polymerase chain reaction, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Child, Preschool, CCAAT-Enhancer-Binding Proteins, Immunoglobulin heavy chain, Female, Inhibitor of Differentiation Proteins, Immunoglobulin Heavy Chains, Fluorescence in situ hybridization
Abstract: Chromosomal translocations involving the immunoglobulin heavy chain locus (IGH@) are recurrent but rare in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and various partner genes have been described. Here, we report a new series of 29 cases of BCP-ALL with IGH@ translocations. The partner gene was identified by fluorescence in situ hybridization and/or molecular cloning in 20 patients. Members of the CEBP gene family (n = 11), BCL2 (n = 3), ID4 (n = 3), EPOR (n = 2), and TRA/D@ (n = 1) were identified and demonstrated by quantitative real-time reverse transcriptase-polymerase chain reaction to be markedly up-regulated. The present cases, added to those already reported, confirm the diversity of the partner genes, which, apart from BCL2, are specific to BCP-ALL. Collectively, patients with IGH@ translocations may represent a novel sub-group of BCP-ALL occurring in adolescents and young adults.
Published: 2013
Full Text: View/download PDF

42. Cytogenetics in the management of lymphomas and lymphoproliferative disorders in adults and children: an update by the Groupe francophone de cytogénétique hématologique (GFCH)

Author: Nathalie Nadal, Christine Lefebvre, Hélène-Antoine Poirel, Evelyne Callet-Bauchu, Dominique Penther, and Elise Chapiro
Subjects: Adult, medicine.medical_specialty, Hematology, Lymphoma, Cytogenetics, Lymphoproliferative disorders, Karyotype, General Medicine, Disease, Biology, medicine.disease, Lymphoproliferative Disorders, Germline mutation, hemic and lymphatic diseases, Internal medicine, Cytogenetic Analysis, medicine, Cancer research, Humans, France, Differential diagnosis, Child, Societies, Medical
Abstract: Non-Hodgkin's lymphomas and lymphoproliferative disorders include a high number of heterogeneous entities, described in the 2008 WHO classification. This classification reflects the crucial role of a multidisciplinary approach which integrates cytogenetic results both for the notion of clonality and for differential diagnosis between these entities. The prognostic impact of some cytogenetic abnormalities or genome complexity is also confirmed for many of these entities. Novel provisional entities have been described, such as BCLU (B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) for which karyotype is critical to distinguish BCLU from Burkitt's lymphoma. The karyotype can be established from any tumour or liquid infiltrated by lymphoma cells. Recent adaptations of technics for cellular cultures according to the subtype of known (or suspected) lymphoma have significantly improved the percentage of informative karyotypes. Conventional karyotypes remain the best technical approach recommended for most of these subtypes. Interphase and/or metaphase FISH also represents a solid and rapid approach, because of the significant number of recurrent (sometimes specific) rearrangements of these entities. Next generation sequencing technologies contribute to enrich genomic data and substantially improve the understanding of oncogenic mechanisms underlying these lymphoid malignancies. Some molecular biomarkers are already part of the diagnostic process (for example, somatic mutation of MYD88 in Waldenstrom disease) thus reinforcing the essential principle of a multidisciplinary approach for the diagnosis of all the mature lymphoid malignancies.
Published: 2016

43. Cytogenetics in the management of hematologic malignancies: an update by the Groupe francophone de cytogénétique hématologique (GFCH)

Author: Agnès Daudignon, Isabelle Luquet, Dominique Penther, Virginie Eclache, Christine Lefebvre, Marina Lafage-Pochitaloff, and Florence Nguyen-Khac
Subjects: Oncology, medicine.medical_specialty, business.industry, Cytogenetics, General Medicine, Disease, Hematology, Gene mutation, Internal medicine, Hematologic Neoplasms, Cytogenetic Analysis, medicine, Humans, France, business, Societies, Medical
Abstract: Cytogenetic analysis is still important in the management of many hematological malignancies, despite the new techniques available such as the high-throughput sequencing analysis, and the discovery of many acquired gene mutations in these diseases. The Groupe francophone de cytogenetique hematologique (GFCH) published in 2004 the recommendations for the cytogenetic management of hematological malignancies. It reports here the update of these recommendations, with a review of the literature for each disease.
Published: 2016

44. Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B-cell lymphomas

Author: David, Rizzo, Pierre-Julien, Viailly, Sylvain, Mareschal, Elodie, Bohers, Jean-Michel, Picquenot, Dominique, Penther, Sydney, Dubois, Vinciane, Marchand, Philippe, Bertrand, Catherine, Maingonnat, Pascaline, Etancelin, Jean, Feuillard, Christian, Bastard, Hervé, Tilly, Fabrice, Jardin, and Philippe, Ruminy
Subjects: Clonal Evolution, Genes, Immunoglobulin Heavy Chain, High-Throughput Nucleotide Sequencing, Humans, Lymphoma, Large B-Cell, Diffuse, Sequence Analysis, DNA, Neoplasm Recurrence, Local, Immunoglobulin Heavy Chains, Phylogeny, V(D)J Recombination, Retrospective Studies
Abstract: Little is known on the phylogenetic relationship between diagnostic and relapse clones of diffuse large B-cell lymphoma (DLBCL). We applied high throughput sequencing (HTS) of the VDJ locus of Immunoglobulin heavy chain (IGHV) on 14 DLBCL patients with serial samples, including tumor biopsies and/or peripheral blood mononuclear cells (PBMC). Phylogenetic data were consolidated with targeted sequencing and cytogenetics. Phylogeny clearly showed that DLBCL relapse could occur according either an early or a late divergent mode. These two modes of divergence were independent from the elapsed time between diagnosis and relapse. We found no significant features for antigen selection pressure in complementary determining region both at diagnosis and relapse for 9/12 pairs and a conserved negative selection pressure for the three remaining cases. Targeted HTS and conventional cytogenetics revealed a branched vs. linear evolution for 5/5 IGHV early divergent cases, but unexpected such "oncogenetic" branched evolution could be found in at least 2/7 IGHV late divergent cases. Thus, if BCR signaling is mandatory for DLBCL emergence, oncogenetic events under chemotherapy selection pressure may be the main driving forces at relapse. Finally, circulating subclones with divergent IGHV somatic hypermutations patterns from initial biopsy could be detected in PBMC at diagnosis for 4/6 patients and, for two of them, at least one was similar to the ones found at relapse. This study highlights that oncogenetic intraclonal diversity of DLBCL should be evaluated beyond the scope a single biopsy and represents a rationale for future investigations using peripheral blood for lymphoid malignancies genotyping. Am. J. Hematol. 92:68-76, 2017. © 2016 Wiley Periodicals, Inc.
Published: 2016

45. Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms

Author: Florence Nguyen-Khac, Sophie Park, Isabelle Templier, Martine Chauvet, Joel Plumas, Julie Charles, Dominique Leroux, Christine Lefebvre, Sophie Rousseaux, Sieme Hamaidia, François-Loïc Cosset, Els Verhoeyen, Mary Callanan, Dominique Penther, Marie-Christine Jacob, Thierry Bonnefoix, Isabelle Luquet, Sarah Bertrand, Anne Roggy, Cornelis P. Tensen, Elizabeth Macintyre, Anouk Emadali, Neda Hoghoughi, Elisabeth Brambilla, Remy Gressin, Laurence Chaperot, Azadeh Hajmirza, Takahiro Maeda, Christophe Roumier, Philippe Bertrand, Céline Suchaud-Martin, Francine Garnache, Christian Bastard, Samuel Duley, Cristina Mecucci, Fabrice Jardin, Juliana Bruder-Costa, Véronique Josserand, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU de Grenoble-Alpes, Graduate School of Biomedical Sciences [Nagasaki University, Japan], Nagasaki University, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Leiden University Medical Center (LUMC), Perugia University School of Medicine, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Universiteit Leiden, Università degli Studi di Perugia = University of Perugia (UNIPG), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (Equipe EVIR), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté]), and Groupe hospitalier Pitié- Salpêtrière, AP-HP
Subjects: 0301 basic medicine, Adult, Skin Neoplasms, Adolescent, Immunology, Plasmacytoid dendritic cell, Haploinsufficiency, Biology, Biochemistry, 03 medical and health sciences, Young Adult, Receptors, Glucocorticoid, medicine, Tumor Cells, Cultured, Humans, Neoplasm Invasiveness, Child, Gene, Aged, Genetics, Regulation of gene expression, Aged, 80 and over, Leukemia, Myeloid Neoplasia, Gene Expression Regulation, Leukemic, Point mutation, hemic and immune systems, Hematology, Cell Biology, Dendritic Cells, Middle Aged, medicine.disease, Non-coding RNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Gene expression profiling, stomatognathic diseases, 030104 developmental biology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA, Long Noncoding
Abstract: International audience; Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressiveleukemia for which knowledge on disease mechanisms and effective therapies are currentlylacking. Only a handful of recurring genetic mutations have been identified and none isspecific to BPDCN. In this study, through molecular cloning in an index case that presenteda balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, weidentify monoallelic deletion of NR3C1 (5q31), encoding the glucocorticoid receptor (GCR),in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including10 with NR3C1 deletion, did not reveal NR3C1 point mutations or indels. Haploinsufficiencyfor NR3C1 defined a subset of BPDCN with lowered GCR expression and extremely pooroverall survival (P 5 .0006). Consistent with a role for GCR in tumor suppression, functionalanalyses coupled with gene expression profiling identified corticoresistance and loss-ofEZH2 function as major downstream consequences of NR3C1 deletion in BPDCN.Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion of NR3C1 to along noncoding RNA (lncRNA) gene (lincRNA-3q) that encodes a novel, nuclear, noncodingRNA involved in the regulation of leukemia stem cell programs and G1/S transition, via E2F.Overexpression oflincRNA-3qwas a consistent feature ofmalignant cells and could be abrogated by bromodomain and extraterminal domain(BET) protein inhibition. Taken together, this work points to NR3C1 as a haploinsufficient tumor suppressor in a subset of BPDCN andidentifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN. (
Published: 2016
Full Text: View/download PDF

46. NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis

Author: Isabelle Radford-Weiss, Arnaud Petit, Audrey Bidet, Dominique Penther, Wendy Cuccuini, M Pasquet, Guy Leverger, Marie-Pierre Pages, Eric Delabesse, Christine Lefebvre, Collonge-Rame Ma, Bart-Delabesse E, Stéphanie Struski, Marina Lafage-Pochitaloff, Isabelle Luquet, Cyril Broccardo, Puiseux C, Nathalie Nadal, Baptiste Gaillard, Naïs Prade, Pierre Bories, Carine Gervais, Carole Barin, Catherine Roche-Lestienne, Francine Mugneret, and Stéphanie Lagarde
Subjects: 0301 basic medicine, Male, Cancer Research, Myeloid, Oncogene Proteins, Fusion, Biology, Translocation, Genetic, Epigenesis, Genetic, Fusion gene, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, hemic and lymphatic diseases, CEBPA, medicine, Biomarkers, Tumor, Humans, Exome, Child, WT1 Proteins, Exome sequencing, Alleles, In Situ Hybridization, Fluorescence, NUP98 Gene, Gene Expression Regulation, Leukemic, breakpoint cluster region, Infant, Newborn, High-Throughput Nucleotide Sequencing, Infant, Hematology, medicine.disease, Prognosis, Nuclear Pore Complex Proteins, Leukemia, Leukemia, Myeloid, Acute, 030104 developmental biology, medicine.anatomical_structure, Oncology, fms-Like Tyrosine Kinase 3, 030220 oncology & carcinogenesis, Child, Preschool, Mutation, Cancer research, CCAAT-Enhancer-Binding Proteins, Female, Signal Transduction
Abstract: Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1. These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations (FLT3 ITD, WT1, CEBPA, NBPF14, BCR and ODF1). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98-rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.
Published: 2016

47. Multiplexed targeted sequencing of recurrent fusion genes in acute leukaemia

Author: Emilie Lemasle, Marie Cornic, Vannier Jp, Pierre-Julien Viailly, Dominique Penther, Sydney Dubois, Stéphane Leprêtre, N. Buchbinder, Camus, Fabrice Jardin, Girod C, Philippe Ruminy, Philippe Bertrand, Sylvain Mareschal, Jean-Michel Picquenot, Pascale Schneider, Larson T, G Buchonnet, David Rizzo, Joly B, Pascaline Etancelin, Angot E, Christian Bastard, Elodie Bohers, Marchand, Hervé Tilly, Florian Clatot, Mathieu Viennot, Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Argelander-Institut für Astronomie (AlfA), and Rheinische Friedrich-Wilhelms-Universität Bonn
Subjects: 0301 basic medicine, Cancer Research, Oncogene Proteins, Oncogene Proteins, Fusion, Chromosomes, Human, Pair 21, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Chromosomal translocation, Biology, Translocation, Genetic, Fusion gene, 03 medical and health sciences, Text mining, Humans, Base sequence, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Genetics, Chromosomes, Human, Pair 15, Leukemia, Base Sequence, business.industry, Reverse Transcriptase Polymerase Chain Reaction, High-Throughput Nucleotide Sequencing, Hematology, 030104 developmental biology, Oncology, Acute Disease, Cytogenetic Analysis, Biological Assay, business, Oligonucleotide Probes, Chromosomes, Human, Pair 17
Abstract: International audience
Published: 2016
Full Text: View/download PDF

48. Patterns of genomic aberrations suggest that Burkitt lymphomas with complex karyotype are distinct from other aggressive B-cell lymphomas withMYCrearrangement

Author: Christian Herens, Christine Terré, Jean-Luc Laï, Marie-Agnès Collonge-Rame, Christine Cabrol, Martine Raphael, Evelyne Callet-Bauchu, Ivan Théate, Jeanne-Marie Libouton, Nicole Dastugue, Carole Barin, Geneviève Ameye, Eric Lippert, Anne Hagemeijer, Lucienne Michaux, Hélène Poirel, Nathalie Nadal, Francine Mugneret, Isabelle Tigaud, Dominique Penther, Laurence Baranger, and Violaine Havelange
Subjects: Male, Cancer Research, Lymphoma, B-Cell, Adolescent, Genes, myc, Abnormal Karyotype, Chromosomal translocation, Biology, immune system diseases, hemic and lymphatic diseases, Complex Karyotype, Genetics, medicine, Chromosomes, Human, Humans, Child, In Situ Hybridization, Fluorescence, B cell, Chromosome Aberrations, Gene Rearrangement, medicine.diagnostic_test, Chromosome, Karyotype, Gene rearrangement, medicine.disease, Burkitt Lymphoma, Lymphoma, medicine.anatomical_structure, Child, Preschool, Immunology, Cancer research, Female, Fluorescence in situ hybridization
Abstract: We previously showed that complex karyotypes (CK) and chromosome 13q abnormalities have an adverse prognostic impact in childhood Burkitt lymphomas/leukemias (BL) and diffuse large B-cell lymphomas (DLBCL). The aim of our study was to identify recurrent alterations associated with MYC rearrangements in aggressive B-cell lymphomas with CK. Multicolor fluorescence in situ hybridization (M-FISH) was performed in 84 patient samples (59 adults and 25 children), including 37 BL (13 lymphomas and 24 acute leukemias), 12 DLBCL, 28 B-cell lymphomas with intermediate features (DLBCL/BL), 4 B-cell precursor acute lymphoblastic leukemias (BCP-ALL), and 3 unclassifiable B-cell lymphomas. New (cytogenetically undetected) abnormalities were identified in 80% of patients. We also refined one-third of the chromosomal aberrations detected by karyotyping. M-FISH proved to be more useful in identifying chromosomal partners involved in unbalanced translocations and in revealing greater complexity of 13q rearrangements. Most of the newly identified or refined recurrent alterations involved 1q, 13q and 3q (gains/losses), 7q and 18q (gains), or 6q (losses), suggesting that these secondary aberrations may play a role in lymphomagenesis. Several patterns of genomic aberrations were identified: 1q gains in BL, trisomies 7 in DLBCL, and 18q-translocations in adult non-BL. BCP-ALL usually displayed an 18q21 rearrangement. BL karyotypes were less complex and aneuploid than those of other MYC-rearranged lymphomas. BCP-ALL and DLBCL/BL were associated with a higher rate of early death than BL and DLBCL. These findings support the categorization of DLBCL/BL as a distinct entity and suggest that BL with CK are indeed different from other aggressive MYC-rearranged lymphomas, which usually show greater genetic complexity. © 2012 Wiley Periodicals, Inc.
Published: 2012
Full Text: View/download PDF

49. Impact of Cytogenetics on Outcome after Allogeneic Transplantation for Myelodysplastic Syndrome or Post MDS Secundary Myeloid Leukemia

Author: P. Etancelin, B. Marcq, Hervé Tilly, Hélène Lanic, Pascal Lenain, Aspasia Stamatoullas, Anne-Lise Menard, Dominique Penther, Christian Bastard, Stéphane Leprêtre, P. Lebreton, Emilie Lemasle, I. Rezine, Nathalie Contentin, and Fabrice Jardin
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Allogeneic transplantation, business.industry, Internal medicine, medicine, Cytogenetics, Myeloid leukemia, Hematology, business
Published: 2017
Full Text: View/download PDF

50. TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm

Author: Françoise Parmentier, Iona Vaida, Dominique Penther, Jean Pierre Marolleau, Philippe Ruminy, Jean-Michel Picquenot, Xavier Troussard, Philippe Courville, Stéphane Leprêtre, Hervé Tilly, Anne Benedicte Duval, Aspasia Stamatoullas, Christian Bastard, Fabrice Jardin, and Jean-Claude Capiod
Subjects: medicine.medical_specialty, Mutation, Hematology, Tumor suppressor gene, Plasmacytoid dendritic cell, Dendritic cell, Blastic plasmacytoid dendritic cell neoplasm, Biology, Tp53 mutation, medicine.disease_cause, Internal medicine, medicine, Cancer research, Antigen-presenting cell
Published: 2011
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

96 results on '"Dominique Penther"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources