128 results on '"Clot, Guillem"'
Search Results
2. SOX11/PRDX2 axis modulates redox homeostasis and chemoresistance in aggressive mantle cell lymphoma
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De Bolòs, Anna, Sureda-Gómez, Marta, Carreras-Caballé, Maria, Rodríguez, Marta-Leonor, Clot, Guillem, Beà, Silvia, Giné, Eva, Campo, Elias, Balsas, Patricia, and Amador, Virginia
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- 2024
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3. SOX11 expression is restricted to EBV-negative Burkitt lymphoma and is associated with molecular genetic features
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Sureda-Gómez, Marta, Iaccarino, Ingram, De Bolòs, Anna, Meyer, Mieke, Balsas, Patricia, Richter, Julia, Rodríguez, Marta-Leonor, López, Cristina, Carreras-Caballé, Maria, Glaser, Selina, Nadeu, Ferran, Jares, Pedro, Clot, Guillem, Siciliano, Maria Chiara, Bellan, Cristiana, Tornambè, Salvatore, Boccacci, Roberto, Leoncini, Lorenzo, Campo, Elias, Siebert, Reiner, Amador, Virginia, and Klapper, Wolfram
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- 2024
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4. Unraveling the genetics of transformed splenic marginal zone lymphoma
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Grau, Marta, López, Cristina, Navarro, Alba, Frigola, Gerard, Nadeu, Ferran, Clot, Guillem, Bastidas-Mora, Gabriela, Alcoceba, Miguel, Baptista, Maria Joao, Blanes, Margarita, Colomer, Dolors, Costa, Dolors, Domingo-Domènech, Eva, Enjuanes, Anna, Escoda, Lourdes, Forcada, Pilar, Giné, Eva, Lopez-Guerra, Mónica, Ramón, Olga, Rivas-Delgado, Alfredo, Vicente Folch, Laura, Wotherspoon, Andrew, Climent, Fina, Campo, Elias, López-Guillermo, Armando, Matutes, Estella, and Beà, Sílvia
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- 2023
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5. Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
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Nadeu, Ferran, Royo, Romina, Massoni-Badosa, Ramon, Playa-Albinyana, Heribert, Garcia-Torre, Beatriz, Duran-Ferrer, Martí, Dawson, Kevin J., Kulis, Marta, Diaz-Navarro, Ander, Villamor, Neus, Melero, Juan L., Chapaprieta, Vicente, Dueso-Barroso, Ana, Delgado, Julio, Moia, Riccardo, Ruiz-Gil, Sara, Marchese, Domenica, Giró, Ariadna, Verdaguer-Dot, Núria, Romo, Mónica, Clot, Guillem, Rozman, Maria, Frigola, Gerard, Rivas-Delgado, Alfredo, Baumann, Tycho, Alcoceba, Miguel, González, Marcos, Climent, Fina, Abrisqueta, Pau, Castellví, Josep, Bosch, Francesc, Aymerich, Marta, Enjuanes, Anna, Ruiz-Gaspà, Sílvia, López-Guillermo, Armando, Jares, Pedro, Beà, Sílvia, Capella-Gutierrez, Salvador, Gelpí, Josep Ll., López-Bigas, Núria, Torrents, David, Campbell, Peter J., Gut, Ivo, Rossi, Davide, Gaidano, Gianluca, Puente, Xose S., Garcia-Roves, Pablo M., Colomer, Dolors, Heyn, Holger, Maura, Francesco, Martín-Subero, José I., and Campo, Elías
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- 2022
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6. Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease
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Nann, Dominik, Ramis-Zaldivar, Joan Enric, Müller, Inga, Gonzalez-Farre, Blanca, Schmidt, Janine, Egan, Caoimhe, Salmeron-Villalobos, Julia, Clot, Guillem, Mattern, Sven, Otto, Franziska, Mankel, Barbara, Colomer, Dolors, Balagué, Olga, Szablewski, Vanessa, Lome-Maldonado, Carmen, Leoncini, Lorenzo, Dojcinov, Stefan, Chott, Andreas, Copie-Bergman, Christiane, Bonzheim, Irina, Fend, Falko, Jaffe, Elaine S., Campo, Elias, Salaverria, Itziar, and Quintanilla-Martinez, Leticia
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- 2020
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7. The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
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Duran-Ferrer, Martí, Clot, Guillem, Nadeu, Ferran, Beekman, Renée, Baumann, Tycho, Nordlund, Jessica, Marincevic-Zuniga, Yanara, Lönnerholm, Gudmar, Rivas-Delgado, Alfredo, Martín, Silvia, Ordoñez, Raquel, Castellano, Giancarlo, Kulis, Marta, Queirós, Ana C., Lee, Seung-Tae, Wiemels, Joseph, Royo, Romina, Puiggrós, Montserrat, Lu, Junyan, Giné, Eva, Beà, Sílvia, Jares, Pedro, Agirre, Xabier, Prosper, Felipe, López-Otín, Carlos, Puente, Xosé S., Oakes, Christopher C., Zenz, Thorsten, Delgado, Julio, López-Guillermo, Armando, Campo, Elías, and Martín-Subero, José Ignacio
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- 2020
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8. Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation
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Vilarrasa-Blasi, Roser, Soler-Vila, Paula, Verdaguer-Dot, Núria, Russiñol, Núria, Di Stefano, Marco, Chapaprieta, Vicente, Clot, Guillem, Farabella, Irene, Cuscó, Pol, Kulis, Marta, Agirre, Xabier, Prosper, Felipe, Beekman, Renée, Beà, Silvia, Colomer, Dolors, Stunnenberg, Hendrik G., Gut, Ivo, Campo, Elias, Marti-Renom, Marc A., and Martin-Subero, José Ignacio
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- 2021
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9. Reproducibility of histologic prognostic parameters for mantle cell lymphoma: cytology, Ki67, p53 and SOX11
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Croci, Giorgio A., Hoster, Eva, Beà, Sílvia, Clot, Guillem, Enjuanes, Anna, Scott, David W., Cabeçadas, José, Veloza, Luis, Campo, Elias, Clasen-Linde, Erik, Goswami, Rashmi S., Helgeland, Lars, Pileri, Stefano, Rymkiewicz, Grzegorz, Reinke, Sarah, Dreyling, Martin, and Klapper, Wolfram
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- 2020
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10. CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma
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Martín-Garcia, David, Navarro, Alba, Valdés-Mas, Rafael, Clot, Guillem, Gutiérrez-Abril, Jesús, Prieto, Miriam, Ribera-Cortada, Inmaculada, Woroniecka, Renata, Rymkiewicz, Grzegorz, Bens, Susanne, de Leval, Laurence, Rosenwald, Andreas, Ferry, Judith A., Hsi, Eric D., Fu, Kai, Delabie, Jan, Weisenburger, Dennis, de Jong, Daphne, Climent, Fina, O'Connor, Sheila J., Swerdlow, Steven H., Torrents, David, Beltran, Sergi, Espinet, Blanca, González-Farré, Blanca, Veloza, Luis, Costa, Dolors, Matutes, Estella, Siebert, Reiner, Ott, German, Quintanilla-Martinez, Leticia, Jaffe, Elaine S., López-Otín, Carlos, Salaverria, Itziar, Puente, Xose S., Campo, Elias, and Beà, Sílvia
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- 2019
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11. Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma
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Yi, Shuhua, Yan, Yuting, Jin, Meiling, Bhattacharya, Supriyo, Wang, Yi, Wu, Yiming, Yang, Lu, Gine, Eva, Clot, Guillem, Chen, Lu, and Yu, Ying
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Gene mutations -- Research ,Leukemia research ,Mantle cell lymphoma -- Genetic aspects -- Development and progression -- Patient outcomes ,Molecular evolution -- Research ,Health care industry - Abstract
Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed a comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal samples from 16 patients and matched RNA-Seq data from 48 samples. We classified MCL into 4 robust clusters (C1--C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation, amp(11q13), and active B cell receptor (BCR) signaling. C2 was enriched with del(11q)/ATM mutations and upregulation of NF-[kappa]B and DNA repair pathways. C3 was characterized by mutations in SP140, NOTCH1, and NSD2, with downregulation of BCR signaling and MYC targets. C4 harbored del(17p)/TP53 mutations, del(13q), and del(9p), and active MYC pathway and hyperproliferation signatures. Patients in these 4 clusters had distinct outcomes (5-year overall survival [OS] rates for C1--C4 were 100%, 56.7%, 48.7%, and 14.2%, respectively). We also inferred the temporal order of genetic events and studied clonal evolution of 16 patients before treatment and at progression/relapse. Eleven of these samples showed drastic clonal evolution that was associated with inferior survival, while the other samples showed modest or no evolution. Our study thus identifies genetic subsets that clinically define this malignancy and delineates clonal evolution patterns and their impact on clinical outcomes., Introduction Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's B cell lymphoma that has a median overall survival (OS) of approximately 5 years (1-7). MCL can generally be [...]
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- 2022
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12. A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome
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Clot, Guillem, Jares, Pedro, Giné, Eva, Navarro, Alba, Royo, Cristina, Pinyol, Magda, Martín-Garcia, David, Demajo, Santiago, Espinet, Blanca, Salar, Antonio, Ferrer, Ana, Muntañola, Ana, Aymerich, Marta, Rauert-Wunderlich, Hilka, Jaffe, Elaine S., Connors, Joseph M., Gascoyne, Randy D., Delabie, Jan, López-Guillermo, Armando, Ott, German, Wright, George W., Staudt, Louis M., Rosenwald, Andreas, Scott, David W., Rimsza, Lisa M., Beà, Sílvia, and Campo, Elías
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- 2018
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13. Robust identification of conventional and leukemic nonnodal mantle cell lymphomas using epigenetic biomarkers.
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Bühler, Marco M., Kulis, Marta, Duran-Ferrer, Martí, López, Cristina, Clot, Guillem, Nadeu, Ferran, Romo, Mònica, Giné, Eva, López-Guillermo, Armando, Beà, Sílvia, Campo, Elías, and Martín-Subero, José Ignacio
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- 2024
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14. Evaluation of clinical parameters and biomarkers in older, untreated mantle cell lymphoma patients receiving bendamustine–rituximab.
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Ramsower, Colleen A., Rosenthal, Allison, Robetorye, Ryan S., Mwangi, Raphael, Maurer, Matthew, Villa, Diego, McDonnell, Tim, Feldman, Andrew, Cohen, Jonathon B., Habermann, Thomas, Campo, Elias, Clot, Guillem, Bühler, Marco M., Kulis, Marta, Martin‐Subero, Jose Ignacio, Giné, Eva, Cook, James R., Hill, Brian, Raess, Philipp W., and Beiske, Klaus H.
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MANTLE cell lymphoma ,RITUXIMAB ,OLDER patients ,SURVIVAL rate ,BIOMARKERS - Abstract
Summary: Mantle cell lymphoma (MCL) is clinically and biologically heterogeneous. While various prognostic features have been proposed, none currently impact therapy selection, particularly in older patients, for whom treatment is primarily dictated by age and comorbidities. Herein, we undertook a comprehensive comparison of clinicopathological features in a cohort of patients 60 years and older, uniformly treated with bendamustine and rituximab, with a median survival of >8 years. The strongest prognostic indicators in this cohort were a high‐risk call by a simplified MCL international prognostic index (s‐MIPI) (HR: 3.32, 95% CI: 1.65–6.68 compared to low risk), a high‐risk call by MCL35 (HR: 10.34, 95% CI: 2.37–45.20 compared to low risk) and blastoid cytology (HR: 4.21, 95% CR: 1.92–9.22 compared to classic). Patients called high risk by both the s‐MIPI and MCL35 had the most dismal prognosis (HR: 11.58, 95% CI: 4.10–32.72), while those with high risk by either had a moderate but clinically relevant prognosis (HR: 2.95, 95% CI: 1.49–5.82). A robust assay to assess proliferation, such as MCL35, along with stringent guidelines for cytological evaluation of MCL, in combination with MIPI, may be a strong path to risk‐stratify older MCL patients in future clinical trials. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Cyclin D1 overexpression induces global transcriptional downregulation in lymphoid neoplasms
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Albero, Robert, Enjuanes, Anna, Demajo, Santiago, Castellano, Giancarlo, Pinyol, Magda, Garcia, Noelia, Capdevila, Cristina, Clot, Guillem, Suarez-Cisneros, Helena, Shimada, Mariko, Karube, Kennosuke, Lopez-Guerra, Monica, Colomer, Dolors, Bea, Silvia, Martin-Subero, Jose Ignacio, Campo, Elias, and Jares, Pedro
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Cancer genetics -- Research ,Cyclin D -- Physiological aspects -- Health aspects ,Cancer research ,Mantle cell lymphoma -- Genetic aspects ,Transcription (Genetics) -- Health aspects ,Health care industry - Abstract
Cyclin D1 is an oncogene frequently overexpressed in human cancers that has a dual function as cell cycle and transcriptional regulator, although the latter is widely unexplored. Here, we investigated the transcriptional role of cyclin D1 in lymphoid tumor cells with cyclin D1 oncogenic overexpression. Cyclin D1 showed widespread binding to the promoters of most actively transcribed genes, and the promoter occupancy positively correlated with the transcriptional output of targeted genes. Despite this association, the overexpression of cyclin D1 in lymphoid cells led to a global transcriptional downmodulation that was proportional to cyclin D1 levels. This cyclin D1-dependent global transcriptional downregulation was associated with a reduced nascent transcription and an accumulation of promoter-proximal paused RNA polymerase II (Pol II) that colocalized with cyclin D1. Concordantly, cyclin D1 overexpression promoted an increase in the Poll II pausing index. This transcriptional impairment seems to be mediated by the interaction of cyclin D1 with the transcription machinery. In addition, cyclin D1 overexpression sensitized cells to transcription inhibitors, revealing a synthetic lethality interaction that was also observed in primary mantle cell lymphoma cases. This finding of global transcriptional dysregulation expands the known functions of oncogenic cyclin D1 and suggests the therapeutic potential of targeting the transcriptional machinery in cyclin D1-overexpressing tumors., Introduction Cyclin D1 plays a central role in cell cycle regulation, and it is frequently upregulated in cancer by different genomic alterations, including amplifications in breast and respiratory tract tumors [...]
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- 2018
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16. The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia
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Beekman, Renée, Chapaprieta, Vicente, Russiñol, Núria, Vilarrasa-Blasi, Roser, Verdaguer-Dot, Núria, Martens, Joost H. A., Duran-Ferrer, Martí, Kulis, Marta, Serra, François, Javierre, Biola M., Wingett, Steven W., Clot, Guillem, Queirós, Ana C., Castellano, Giancarlo, Blanc, Julie, Gut, Marta, Merkel, Angelika, Heath, Simon, Vlasova, Anna, Ullrich, Sebastian, Palumbo, Emilio, Enjuanes, Anna, Martín-García, David, Beà, Sílvia, Pinyol, Magda, Aymerich, Marta, Royo, Romina, Puiggros, Montserrat, Torrents, David, Datta, Avik, Lowy, Ernesto, Kostadima, Myrto, Roller, Maša, Clarke, Laura, Flicek, Paul, Agirre, Xabier, Prosper, Felipe, Baumann, Tycho, Delgado, Julio, López-Guillermo, Armando, Fraser, Peter, Yaspo, Marie-Laure, Guigó, Roderic, Siebert, Reiner, Martí-Renom, Marc A., Puente, Xose S., López-Otín, Carlos, Gut, Ivo, Stunnenberg, Hendrik G., Campo, Elias, and Martin-Subero, Jose I.
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- 2018
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17. Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene
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Schmidt, Janine, Gong, Shunyou, Marafioti, Teresa, Mankel, Barbara, Gonzalez-Farre, Blanca, Balagué, Olga, Mozos, Ana, Cabeçadas, José, van der Walt, Jon, Hoehn, Daniela, Rosenwald, Andreas, Ott, German, Dojcinov, Stefan, Egan, Caoimhe, Nadeu, Ferran, Ramis-Zaldívar, Joan Enric, Clot, Guillem, Bárcena, Carmen, Pérez-Alonso, Vanesa, Endris, Volker, Penzel, Roland, Lome-Maldonado, Carmen, Bonzheim, Irina, Fend, Falko, Campo, Elias, Jaffe, Elaine S., Salaverria, Itziar, and Quintanilla-Martinez, Leticia
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- 2016
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18. Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics
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Speedy, Helen E., Beekman, Renée, Chapaprieta, Vicente, Orlando, Giulia, Law, Philip J., Martín-García, David, Gutiérrez-Abril, Jesús, Catovsky, Daniel, Beà, Sílvia, Clot, Guillem, Puiggròs, Montserrat, Torrents, David, Puente, Xose S., Allan, James M., López-Otín, Carlos, Campo, Elias, Houlston, Richard S., and Martín-Subero, José I.
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- 2019
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19. Genomic landscape of follicular lymphoma across a wide spectrum of clinical behaviors.
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Mozas, Pablo, López, Cristina, Grau, Marta, Nadeu, Ferran, Clot, Guillem, Valle, Sara, Kulis, Marta, Navarro, Alba, Ramis‐Zaldivar, Joan Enric, González‐Farré, Blanca, Rivas‐Delgado, Alfredo, Rivero, Andrea, Frigola, Gerard, Balagué, Olga, Giné, Eva, Delgado, Julio, Villamor, Neus, Matutes, Estella, Magnano, Laura, and García‐Sanz, Ramón
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FOLLICULAR lymphoma ,NUCLEOTIDE sequencing ,LYMPHOID tissue ,PROTEIN models ,GENOMICS - Abstract
While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1–3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non‐relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS). We identified six focal driver losses (1p36.32, 6p21.32, 6q14.1, 6q23.3, 9p21.3, 10q23.33) and 1p36.33 copy‐neutral loss of heterozygosity (CN‐LOH). By integrating CNA and NGS results, the most frequently altered genes/regions were KMT2D (79%), CREBBP (67%), TNFRSF14 (46%) and BCL2 (40%). Although we found that mutations in PIM1, FOXO1 and TMEM30A were associated with an adverse clinical behavior, definitive conclusions cannot be drawn, due to the small sample size. We identified common precursor cells harboring early oncogenic alterations of the KMT2D, CREBBP, TNFRSF14 and EP300 genes and 16p13.3‐p13.2 CN‐LOH. Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma
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Beà, Sílvia, Valdés-Mas, Rafael, Navarro, Alba, Salaverria, Itziar, Martín-Garcia, David, Jares, Pedro, Giné, Eva, Pinyol, Magda, Royo, Cristina, Nadeu, Ferran, Conde, Laura, Juan, Manel, Clot, Guillem, Vizán, Pedro, Di Croce, Luciano, Puente, Diana A., López-Guerra, Mónica, Moros, Alexandra, Roue, Gael, Aymerich, Marta, Villamor, Neus, Colomo, Lluís, Martínez, Antonio, Valera, Alexandra, Martín-Subero, José I., Amador, Virginia, Hernández, Luis, Rozman, Maria, Enjuanes, Anna, Forcada, Pilar, Muntañola, Ana, Hartmann, Elena M., Calasanz, María J., Rosenwald, Andreas, Ott, German, Hernández-Rivas, Jesús M., Klapper, Wolfram, Siebert, Reiner, Wiestner, Adrian, Wilson, Wyndham H., Colomer, Dolors, López-Guillermo, Armando, López-Otín, Carlos, Puente, Xose S., and Campo, Elías
- Published
- 2013
21. A Comprehensive DNA Methylome Analysis of Stereotyped and Non-Stereotyped CLL Reveals an Epigenetic Signature with Strong Clinical Impact Encompassing IGHV Status, Stereotypes and IGLV3-21R110
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Duran-Ferrer, Martí, Mansouri, Larry, Nadeu, Ferran, Clot, Guillem, Bhoi, Sujata, Ann Sutton, Lesley, Baliakas, Panagiotis, Ek, Sara, Kuci Emruli, Venera, Plevova, Karla, Davis, Zadie, Goransson-Kultima, Hanna, Isaksson, Anders, Smedby, Karin E., Gaidano, Gianluca, Langerak, Anton W., Davi, Frederic, Rossi, Davide, Oscier, David, Pospisilova, Sarka, Karypidou, Maria, Agathangelidis, Andreas, Huber, Wolfgang, Lu, Junyan, Zenz, Thorsten, Delgado, Julio, Lopez-Guillermo, Armando, Ghia, Paolo, Campo, Elías, Stamatopoulos, Kostas, Rosenquist, Richard, and Martín-Subero, José I.
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- 2022
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22. High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma
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Sebastián, Elena, Alcoceba, Miguel, Martín-García, David, Blanco, Óscar, Sanchez-Barba, Mercedes, Balanzategui, Ana, Marín, Luis, Montes-Moreno, Santiago, González-Barca, Eva, Pardal, Emilia, Jiménez, Cristina, García-Álvarez, María, Clot, Guillem, Carracedo, Ángel, Gutiérrez, Norma C., Sarasquete, M. Eugenia, Chillón, Carmen, Corral, Rocío, Prieto-Conde, M. Isabel, Caballero, M. Dolores, Salaverria, Itziar, García-Sanz, Ramón, and González, Marcos
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- 2016
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23. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma
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Vegliante, Maria Carmela, Palomero, Jara, Pérez-Galán, Patricia, Roué, Gaël, Castellano, Giancarlo, Navarro, Alba, Clot, Guillem, Moros, Alexandra, Suárez-Cisneros, Helena, Beà, Sílvia, Hernández, Luis, Enjuanes, Anna, Jares, Pedro, Villamor, Neus, Colomer, Dolors, Martín-Subero, José Ignacio, Campo, Elias, and Amador, Virginia
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- 2013
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24. Non-coding recurrent mutations in chronic lymphocytic leukaemia
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Puente, Xose S., Beà, Silvia, Valdés-Mas, Rafael, Villamor, Neus, Gutiérrez-Abril, Jesús, Martín-Subero, José I., Munar, Marta, Rubio-Pérez, Carlota, Jares, Pedro, Aymerich, Marta, Baumann, Tycho, Beekman, Renée, Belver, Laura, Carrio, Anna, Castellano, Giancarlo, Clot, Guillem, Colado, Enrique, Colomer, Dolors, Costa, Dolors, Delgado, Julio, Enjuanes, Anna, Estivill, Xavier, Ferrando, Adolfo A., Gelpí, Josep L., González, Blanca, González, Santiago, González, Marcos, Gut, Marta, Hernández-Rivas, Jesús M., López-Guerra, Mónica, Martín-García, David, Navarro, Alba, Nicolás, Pilar, Orozco, Modesto, Payer, Ángel R., Pinyol, Magda, Pisano, David G., Puente, Diana A., Queirós, Ana C., Quesada, Víctor, Romeo-Casabona, Carlos M., Royo, Cristina, Royo, Romina, Rozman, María, Russiñol, Nuria, Salaverría, Itziar, Stamatopoulos, Kostas, Stunnenberg, Hendrik G., Tamborero, David, Terol, María J., Valencia, Alfonso, López-Bigas, Nuria, Torrents, David, Gut, Ivo, López-Guillermo, Armando, López-Otín, Carlos, and Campo, Elías
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- 2015
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25. Genome-wide methylation analyses identify a subset of mantle cell lymphoma with a high number of methylated CpGs and aggressive clinicopathological features
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Enjuanes, Anna, Albero, Robert, Clot, Guillem, Navarro, Alba, Beà, Sílvia, Pinyol, Magda, Martín-Subero, José I., Klapper, Wolfram, Staudt, Louis M., Jaffe, Elaine S., Rimsza, Lisa, Braziel, Rita M., Delabie, Jan, Cook, James R., Tubbs, Raymond R., Gascoyne, Randy, Connors, Joseph M., Weisenburger, Dennis D., Greiner, Timothy C., Chan, Wing-Chung, López-Guillermo, Armando, Rosenwald, Andreas, Ott, German, Campo, Elías, and Jares, Pedro
- Published
- 2013
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26. Revised International Prognostic Index and genetic alterations are associated with early failure to R‐CHOP in patients with diffuse large B‐cell lymphoma.
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Dlouhy, Ivan, Karube, Kennosuke, Enjuanes, Anna, Salaverria, Itziar, Nadeu, Ferran, Ramis‐Zaldivar, Juan Enric, Valero, Juan G., Rivas‐Delgado, Alfredo, Magnano, Laura, Martin‐García, David, Pérez‐Galán, Patricia, Clot, Guillem, Rovira, Jordina, Jares, Pedro, Balagué, Olga, Giné, Eva, Mozas, Pablo, Briones, Javier, Sancho, Juan‐Manuel, and Salar, Antonio
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ANTINEOPLASTIC combined chemotherapy protocols ,CELL cycle regulation ,EXTRACELLULAR matrix ,GENE expression profiling ,DIFFUSE large B-cell lymphomas ,TUMOR microenvironment - Abstract
Summary: Relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) cases have a poor outcome. Here we analysed clinico‐biological features in 373 DLBCL patients homogeneously treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R‐CHOP), in order to identify variables associated with early failure to treatment (EF), defined as primary refractoriness or relapse within 12 months from diagnosis. In addition to clinical features, mutational status of 106 genes was studied by targeted next‐generation sequencing in 111 cases, copy number alterations in 87, and gene expression profile (GEP) in 39. Ninety‐seven cases (26%) were identified as EF and showed significantly shorter overall survival (OS). Patients with B symptoms, advanced stage, high levels of serum lactate dehydrogenase (LDH) or β2‐microglobulin, low lymphocyte/monocyte ratio and higher Revised International Prognostic Index (R‐IPI) scores, as well as those with BCL2 rearrangements more frequently showed EF, with R‐IPI being the most important in logistic regression. Mutations in NOTCH2, gains in 5p15·33 (TERT), 12q13 (CDK2), 12q14·1 (CDK4) and 12q15 (MDM2) showed predictive importance for EF independently from R‐IPI. GEP studies showed that EF cases were significantly enriched in sets related to cell cycle regulation and inflammatory response, while cases in response showed over‐representation of gene sets related to extra‐cellular matrix and tumour microenvironment. [ABSTRACT FROM AUTHOR]
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- 2022
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27. Development of a Novel Chromatin Activation Score As a Powerful Independent Prognostic Factor in Chronic Lymphocytic Leukemia
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Chapaprieta, Vicente, Maiques-Diaz, Alba, Clot, Guillem, Nadeu, Ferran, Mateos-Jaimez, Judith, Vidal, Anna, Charalampopoulou, Stella, Duran-Ferrer, Martí, Royo, Romina, Lu, Junyan, Zenz, Thorsten, Delgado, Julio, Lopez-Guillermo, Armando, Campo, Elías, and Martín-Subero, José I.
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- 2022
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28. Whole-Genome Analysis of Histone Modifications Reveals New Insights into the Biology and Clinical Behavior of Mantle Cell Lymphoma Subtypes
- Author
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García-Torre, Beatriz, Kulis, Marta, Romo, Mònica, Vidal, Anna, Charalampopoulou, Stella, Chapaprieta, Vicente, Duran-Ferrer, Martí, Nadeu, Ferran, López, Cristina, Clot, Guillem, Giné, Eva, Lopez-Guillermo, Armando, Beà, Sílvia, Colomer, Dolors, Campo, Elías, and Martín-Subero, José I.
- Published
- 2022
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29. Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in diffuse large B-cell lymphoma
- Author
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Recasens-Zorzo, Clara, Cardesa-Salzmann, Teresa, Petazzi, Paolo, Ros-Blanco, Laia, Esteve-Arenys, Anna, Clot, Guillem, Guerrero-Hernández, Martina, Rodríguez, Vanina, Soldini, Davide, Valera, Alexandra, Moros, Alexandra, Climent, Fina, Gonzalez-Barca, Eva, Mercadal, Santiago, Arenillas, Leonor, Calvo, Xavier, Mate Sanz, Jose Luís, Gutiérrez-García, Gonzalo, Casanova Rigat, Isolda, Mangues, Ramon, Sanjuan-Pla, Alejandra, Bueno, Clara, Menéndez Bujan, Pablo, Martínez, Antonio, Colomer, Dolors, Estrada Tejedor, Roger, Teixidó, Jordi, Campo, Elias, López-Guillermo, A., Borrell, José I, Colomo, Luis, Pérez-Galán, Patricia, Roué, Gaël, Universitat Autònoma de Barcelona, and Universitat de Barcelona
- Subjects
Male ,Receptors, CXCR4 ,Limfomes ,MAP Kinase Signaling System ,medicine.medical_treatment ,Non-Hodgkin Lymphoma ,Biopsy ,Cèl·lules B ,Limfomes -- Tractament ,Article ,03 medical and health sciences ,Chemokine receptor ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,Acetamides ,Medicine ,Animals ,Humans ,Receptor ,Mitogen-Activated Protein Kinase 1 ,B cells ,Mitogen-Activated Protein Kinase 3 ,business.industry ,Hematology ,Azepines ,Cemokine CXCL12 ,medicine.disease ,Xenograft Model Antitumor Assays ,Chemokine CXCL12 ,3. Good health ,Bromodomain ,Lymphoma ,Cytokine ,Tumor progression ,Cancer research ,Female ,Lymphomas ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,Proto-Oncogene Proteins c-akt ,030215 immunology - Abstract
Constitutive activation of the chemokine receptor CXCR4 has be en associated with tumor progression, invasion, and chemotherapy resistance in different cancer subtypes. Although the CXCR4 pathway has recently been suggested as an adverse prognostic marker in diffuse large B-cell lymphoma, its biological relevance in this disease remains underexplored. In a homogeneous set of 52 biopsies from patients, an antibody-based cytokine array showed that tissue levels of CXCL12 correlated with high microvessel density and bone marrow involvement at diagnosis, supporting a role for the CXCL12-CXCR4 axis in disease progression. We then identified the tetra-amine IQS-01.01RS as a potent inverse agonist of the receptor, preventing CXCL12-mediated chemotaxis and triggering apoptosis in a panel of 18 cell lines and primary cultures, with superior mobilizing properties in vivo than those of the standard agent. IQS-01.01RS activity was associated with downregulation of p-AKT, p-ERK1/2 and destabilization of MYC, allowing a synergistic interaction with the bromodomain and extra-terminal domain inhibitor, CPI203. In a xenotransplant model of diffuse large B-cell lymphoma, the combination of IQS-01.01RS and CPI203 decreased tumor burden through MYC and p-AKT downregulation, and enhanced the induction of apoptosis. Thus, our results point out an emerging role of CXCL12-CXCR4 in the pathogenesis of diffuse large B-cell lymphoma and support the simultaneous targeting of CXCR4 and bromodomain proteins as a promising, rationale-based strategy for the treatment of this disease.
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- 2019
30. A low lymphocyte-to-monocyte ratio is an independent predictor of poorer survival and higher risk of histological transformation in follicular lymphoma.
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Mozas, Pablo, Rivero, Andrea, Rivas-Delgado, Alfredo, Nadeu, Ferran, Clot, Guillem, Correa, Juan Gonzalo, Castillo, Carlos, Bataller, Alex, Baumann, Tycho, Giné, Eva, Delgado, Julio, Villamor, Neus, Campo, Elías, Pérez-Galán, Patricia, Magnano, Laura, and López-Guillermo, Armando
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LYMPHOMAS ,PROGRESSION-free survival ,DIAGNOSIS ,PROGNOSIS ,FOLLICULAR lymphoma - Abstract
The lymphocyte-to-monocyte ratio (LMR) is a prognostic factor in different neoplasms, but its potential importance in follicular lymphoma (FL) is not well defined. We studied 384 FL patients for which the LMR was available at diagnosis. Baseline features and outcomes were compared between patients with an LMR ≤/>2.5. The 76 patients (20%) who had an LMR ≤2.5 were older and had a higher tumor burden. A low LMR was predictive of a lower 10-y progression-free survival (32 vs. 55%, p =.001) and overall survival (35 vs. 78%, p <.0001; HR = 2.3, p =.003 in a 6-element multivariable model). A low LMR was also an independent risk factor for histological transformation (11 vs. 6% at 10 years, p =.01). Likewise, patients with a low LMR had a higher rate of second malignancies. The potential utility of this widely available parameter and its contribution to well-established prognostic scores need to be explored in independent, prospective series. [ABSTRACT FROM AUTHOR]
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- 2021
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- View/download PDF
31. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- Author
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Law, Philip J, Berndt, Sonja I, Speedy, Helen E, Camp, Nicola J, Sava, Georgina P, Skibola, Christine F, Holroyd, Amy, Joseph, Vijai, Sunter, Nicola J, Nieters, Alexandra, Bea, Silvia, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R, Clot, Guillem, Teras, Lauren R, Quintela, Inés, Birmann, Brenda M, Jayne, Sandrine, Cozen, Wendy, Majid, Aneela, Smedby, Karin E, Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R., Hall, Andrew G, Purdue, Mark P, Mainou-Fowler, Tryfonia, Vajdic, Claire M, Jackson, Graham H, Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G, Lawrence, Charles, Call, Timothy G, Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W Ryan, Link, Brian K, Conde, Lucia, Bracci, Paige M., Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E., Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Vermeulen, Roel C H, Southey, Melissa C, Milne, Roger L., Clavel, Jacqueline, Topka, Sabine, Spinelli, John J, Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M, Harris, Robert J, Miligi, Lucia, Pettitt, Andrew R, North, Kari E, Allsup, David J, Fraumeni, Joseph F, Bailey, James R, Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Christopher, Chanock, Stephen J, Fegan, Chris, Rosenquist, Richard, de Sanjose, Silvia, Carracedo, Angel, Dyer, Martin J S, Catovsky, Daniel, Campo, Elias, Cerhan, James R., Allan, James M, Rothman, Nathanial, Houlston, Richard, Slager, Susan, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Department of Physics, Loyola College, Nungambakkam, Chennai – 600 034, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Aleppo [Aleppo], Sea Mammal Research Unit [University of St Andrews] (SMRU), School of Biology [University of St Andrews], University of St Andrews [Scotland]-University of St Andrews [Scotland]-Natural Environment Research Council (NERC), Department of Chemical Engineering, Imperial College London, De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), The Cancer Council Victoria, University of Oulu, Uppsala Universitet [Uppsala], Université Paris Nanterre (UPN), University of Iowa [Iowa City], Registre des hémopathies malignes de Côte d'Or, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), B.B. Brodie Department of Neuroscience, Pennsylvania State University (Penn State), Penn State System, University of Newcastle [Australia] (UoN), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Department of Haematology, School of Medicine, Cardiff University, CIBER de Enfermedades Raras (CIBERER), University of Leeds, Haemato-oncology, Institute of cancer research, Mayo Clinic [Rochester], Northern Institute for Cancer Research [Newcastle] (NICR), Newcastle University [Newcastle], Institute of Cancer Research, Belmont, Sutton, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sea Mammal Research Unit, Scottish Oceans Institute, University of St Andrews [Scotland], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Cardiff, Équipe Instrumentation embarquée et systèmes de surveillance intelligents (LAAS-S4M), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), University of Newcastle [Callaghan, Australia] (UoN), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-2, Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Université Fédérale Toulouse Midi-Pyrénées
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Adult ,Male ,RM ,Cancer och onkologi ,B-Lymphocytes ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,Science ,Chromosome Mapping ,Middle Aged ,Leukemia, Lymphocytic, Chronic, B-Cell ,Polymorphism, Single Nucleotide ,Article ,Young Adult ,Cancer and Oncology ,Case-Control Studies ,Antibody Formation ,Chromosomes, Human ,Humans ,Female ,Genetic Predisposition to Disease ,RC ,Genome-Wide Association Study - Abstract
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response., Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.
- Published
- 2017
32. Increased tumour angiogenesis in SOX11‐positive mantle cell lymphoma.
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Petrakis, Georgios, Veloza, Luis, Clot, Guillem, Gine, Eva, Gonzalez‐Farre, Blanca, Navarro, Alba, Bea, Silvia, Martínez, Antonio, Lopez‐Guillermo, Armando, Amador, Virginia, Ribera‐Cortada, Inmaculada, and Campo, Elias
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MANTLE cell lymphoma ,TUMORS ,NEOVASCULARIZATION ,IMAGE analysis - Abstract
Aims: Mantle cell lymphoma (MCL) is a heterogeneous disease with an aggressive behaviour in most cases, which is associated with expression of sex determining region‐Y‐box11 (SOX11). Experimental studies have shown that SOX11 expression is associated with an angiogenic switch characterised by increased expression of angiogenic‐related signatures and vascularisation of murine tumours. However, the relationship between angiogenesis and SOX11 expression in primary tumours is not well understood. Therefore, the aim of this study was to evaluate the development of microvascular angiogenesis in primary MCL in relation to SOX11 expression and its potential prognostic value. Methods and results: Fifty‐six patients diagnosed with MCL, 38 SOX11‐positive and 18 SOX11‐negative, were studied. The relative intratumoral microvascular area (MVA) and microvessel density (MVD) (number of intratumoral microvessels/μm2) were measured on CD34‐stained slides using a computerised image analysis system. SOX11‐positive MCL showed a significant higher microvascular development than negative tumours (median MVA = 14.5 × 10−3 versus 5.0 × 10−3P < 0.001; median MVD = 18.6/μm2 versus 14.2/μm2, P = 0.021). Analysing the MVA and MVD as continuous variables, a high MVD was associated with shorter overall survival (P = 0.004), and a similar tendency was observed for high MVA (P = 0.064). The microvascular development was not related to the Ki‐67 proliferative index or 17p/TP53, 9p or 11q alterations. Conclusions: These findings suggest that SOX11 promotes an angiogenic phenotype in primary MCL, which may contribute to the more aggressive behaviour of these tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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33. Chromosome Banding Analysis Versus Genomic Microarrays: A Comparison of Methods for Genomic Complexity Risk Stratification in Chronic Lymphocytic Leukemia Patients with Complex Karyotype
- Author
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Ramos Campoy, Silvia, Puiggros, Anna, Bea, Silvia, Bougeon, Sandrine, Larrayoz, Maria Jose, Clot, Guillem, Costa, Dolors, Rigolin, Gian Matteo, Ortega, Margarita, Blanco, Laura, Collado, Rosa, Salgado, Rocio N, García-Malo, María-Dolores, Campeny, Andrea, Valiente, Alberto, Nadeu, Ferran, Delgado, Julio, Baumann, Tycho, Ancín, Idoya, Moro García, Marco Antonio, Gimeno, Eva, Moreno, Carol, Bosch, Francesc, Ferrer, Ana, Blanco, Gonzalo, Calasanz, Maria Jose, Cuneo, Antonio, Haferlach, Claudia, Schoumans, Jacqueline, and Espinet, Blanca
- Published
- 2019
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34. Characterization of the DNA Methylome during Human B-Cell Differentiation
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Kulis, Marta, Heath, Simon, Castellano, Giancarlo, Beekman, Renee, Merkel, Angelika, Raineri, Emanuele, Esteve, Anna, Queiros, AnaC, Clot, Guillem, Schuyler, Ronald, Ecker, Simone, Pancaldi, Vera, Rico, Daniel, Agueda, Lidia, Blanc, Julie, Richardson, David, Clarke, Laura, Datta, Avik, Russinol, Nuria, Pascual, Marien, Aguirre, Xavier, Prosper, Felipe, Alignani, Diego, Caron, Gersende, Fest, Thierry, Muench, MarcusO, Fomin, Marina, Lee, Seung-Tae, Wiemels, JosephL, Valencia, Alfonso, Gut, Marta, Flicek, Paul, Stunnenberg, HendrikG, Siebert, Reiner, Küppers, Ralf, Gut, IvoG, Campo, Elias, and Martin-Subero, JoseI
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Medizin - Published
- 2014
35. New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies.
- Author
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Scott, David W., Abrisqueta, Pau, Wright, George W., Slack, Graham W., Mottok, Anja, Villa, Diego, Jares, Pedro, Rauert-Wunderlich, Hilka, Royo, Cristina, Clot, Guillem, Pinyol, Magda, Boyle, Merrill, Fong Chun Chan, Braziel, Rita M., Chan, Wing C., Weisenburger, Dennis D., Cook, James R., Greiner, Timothy C., Fu, Kai, and Ott, German
- Published
- 2017
- Full Text
- View/download PDF
36. NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease.
- Author
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Martinez, Daniel, Navarro, Alba, Martinez-Trillos, Alejandra, Molina-Urra, Ricardo, Gonzalez-Farre, Blanca, Salaverria, Itziar, Nadeu, Ferran, Enjuanes, Anna, Clot, Guillem, Costa, Dolors, Carrio, Ana, Villamor, Neus, Colomer, Dolors, Martinez, Antonio, Bens, Susanne, Siebert, Reiner, Wotherspoon, Andrew, Beà, Sílvia, Matutes, Estella, and Campo, Elias
- Published
- 2016
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- View/download PDF
37. Detection of chromothripsis-like patterns with a custom array platform for chronic lymphocytic leukemia.
- Author
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Salaverria, Itziar, Martín‐Garcia, David, López, Cristina, Clot, Guillem, García‐Aragonés, Manel, Navarro, Alba, Delgado, Julio, Baumann, Tycho, Pinyol, Magda, Martin‐Guerrero, Idoia, Carrió, Ana, Costa, Dolors, Queirós, Ana C., Jayne, Sandrine, Aymerich, Marta, Villamor, Neus, Colomer, Dolors, González, Marcos, López‐Guillermo, Armando, and Campo, Elías
- Published
- 2015
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38. Gene Expression Profiling Signatures Allow the Identification of Unclassifiable Leukemic B-Cell Lymphoid Neoplasms
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Navarro, Alba, Clot, Guillem, Martinez-Trillos, Alejandra, Salaverria, Itziar, Martin-Garcia, David, Trim, Nicola, Fernandez, Veronica, Villamor, Neus, Colomer, Dolors, Pinyol, Magda, Jares, Pedro, Erber, Wendy N., Wiestner, Adrian, Wilson, Wyndham H., Siebert, Reiner, Aymerich, Marta, Lopez-Guillermo, Armando, Sánchez, Àlex, Campo, Elias, Matutes, Estella, and Beà, Sílvia
- Published
- 2015
- Full Text
- View/download PDF
39. Whole-genome fingerprint of the DNA methylome during human B cell differentiation.
- Author
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Kulis, Marta, Queirós, Ana C, Castellano, Giancarlo, Beekman, Renée, Clot, Guillem, Verdaguer-Dot, Néria, Russiñol, Nuria, Vilarrasa-Blasi, Roser, Campo, Elías, Martín-Subero, José I, Caron, Gersende, Fest, Thierry, Muench, Marcus O, Fomin, Marina E, Lee, Seung-Tae, Wiemels, Joseph L, Stunnenberg, Hendrik G, Siebert, Reiner, Küppers, Ralf, and Merkel, Angelika
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HUMAN genome ,DNA analysis ,B cell differentiation ,DNA microarrays ,DNA methylation ,DEMETHYLATION ,AGING - Abstract
We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
40. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- Author
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Law, Philip J., Berndt, Sonja I., Speedy, Helen E., Camp, Nicola J., Sava, Georgina P., Skibola, Christine F., Holroyd, Amy, Joseph, Vijai, Sunter, Nicola J., Nieters, Alexandra, Bea, Silvia, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R., Clot, Guillem, Teras, Lauren R., Quintela, Inés, Birmann, Brenda M., Jayne, Sandrine, Cozen, Wendy, Majid, Aneela, Smedby, Karin E., Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R., Hall, Andrew G., Purdue, Mark P., Mainou-Fowler, Tryfonia, Vajdic, Claire M., Jackson, Graham H., Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G., Lawrence, Charles, Call, Timothy G., Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W Ryan, Link, Brian K., Conde, Lucia, Bracci, Paige M., Holly, Elizabeth A., Jackson, Rebecca D., Tinker, Lesley F., Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E., Morton, Lindsay M., Severson, Richard K., Riboli, Elio, Vineis, Paolo, Vermeulen, Roel C. H., Southey, Melissa C., Milne, Roger L., Clavel, Jacqueline, Topka, Sabine, Spinelli, John J., Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M., Harris, Robert J., Miligi, Lucia, Pettitt, Andrew R., North, Kari E., Allsup, David J., Fraumeni, Joseph F., Bailey, James R., Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Chris, Chanock, Stephen J., Fegan, Chris, Rosenquist, Richard, de Sanjose, Silvia, Carracedo, Angel, Dyer, Martin J. S., Catovsky, Daniel, Campo, Elias, Cerhan, James R., Allan, James M., Rothman, Nathanial, Houlston, Richard, and Slager, Susan
- Abstract
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
- Published
- 2017
- Full Text
- View/download PDF
41. Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia.
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Kulis, Marta, Heath, Simon, Bibikova, Marina, Queirós, Ana C, Navarro, Alba, Clot, Guillem, Martínez-Trillos, Alejandra, Castellano, Giancarlo, Brun-Heath, Isabelle, Pinyol, Magda, Barberán-Soler, Sergio, Papasaikas, Panagiotis, Jares, Pedro, Beà, Sílvia, Rico, Daniel, Ecker, Simone, Rubio, Miriam, Royo, Romina, Ho, Vincent, and Klotzle, Brandy
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DNA methylation ,CHRONIC lymphocytic leukemia ,B cells ,POPULATION genetics ,DNA microarrays ,GENE expression - Abstract
We have extensively characterized the DNA methylomes of 139 patients with chronic lymphocytic leukemia (CLL) with mutated or unmutated IGHV and of several mature B-cell subpopulations through the use of whole-genome bisulfite sequencing and high-density microarrays. The two molecular subtypes of CLL have differing DNA methylomes that seem to represent epigenetic imprints from distinct normal B-cell subpopulations. DNA hypomethylation in the gene body, targeting mostly enhancer sites, was the most frequent difference between naive and memory B cells and between the two molecular subtypes of CLL and normal B cells. Although DNA methylation and gene expression were poorly correlated, we identified gene-body CpG dinucleotides whose methylation was positively or negatively associated with expression. We have also recognized a DNA methylation signature that distinguishes new clinico-biological subtypes of CLL. We propose an epigenomic scenario in which differential methylation in the gene body may have functional and clinical implications in leukemogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
42. Molecular Subsets of Mantle Cell Lymphoma Defined by the IGHV Mutational Status and SOX11 Expression Have Distinct Biologic and Clinical Features.
- Author
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Navarro, Alba, Clot, Guillem, Royo, Cristina, Jares, Pedro, Hadzidimitriou, Anastasia, Agathangelidis, Andreas, Bikos, Vasilis, Darzentas, Nikos, Papadaki, Theodora, Salaverria, Itziar, Pinyol, Magda, Puig, Xavier, Palomero, Jara, Vegliante, Maria Carmela, Amador, Virgina, Martinez-Trillos, Alejandra, Stefancikova, Lenka, Wiestner, Adrian, Wilson, Wyndham, and Pott, Christiane
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- *
LYMPHOMA treatment , *CANCER treatment , *IMMUNOGENETICS , *CANCER genetics , *GENETIC mutation - Abstract
Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course, whereas others having an indolent behavior. We conducted an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B-cell receptors (BcR) may identify different subsets of tumors. Truly unmutated (100% identity) IGHV genes were found in 24% cases, 40% were minimally/borderline mutated (99.9%-97%), 19% significantly mutated (96.9%-95%), and 17% hypermutated (<95%). Tumors with high or low mutational load used different IGHV genes, and their gene expression profiles were also different for several gene pathways. A gene set enrichment analysis showed that MCL with high and low IGHV mutations were enriched in memory and naive B-cell signatures, respectively. Furthermore, the highly mutated tumors had less genomic complexity, were preferentially SOX11-negative, and showed more frequent nonnodal disease. The best cut-off of germline identity of IGHV genes to predict survival was 97%. Patients with high and low mutational load had significant different outcome with 5-year overall survival (OS) of 59% and 40%, respectively (P = 0.004). Nodal presentation and SOX11 expression also predicted for poor OS. In a multivariate analysis, IGHV gene status and SOX11 expression were independent risk factors. In conclusion, these observations suggest the idea that MCL with mutated IGHV, SOX11-negativity, and nonnodal presentation correspond to a subtype of the disease with more indolent behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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43. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
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Clavel, Jacqueline, Harris, Robert J., Boffetta, Paolo, De Sanjose, Silvia, Clot, Guillem, Mansouri, Larry, Campo, Elias, Vineis, Paolo, Giles, Graham G., Slager, Susan, Marr, Helen, Jackson, Rebecca D., Teras, Lauren R., Houlston, Richard, Bracci, Paige M., Quintela, Inés, Conde, Lucia, Bailey, James R., Weinstein, Stephanie, Glimelius, Bengt, Milne, Roger L., Lawrence, Charles, Caporaso, Neil E., Kraft, Peter, Holly, Elizabeth A., Berndt, Sonja I., Hjalgrim, Henrik, McKay, James, Rothman, Nathanial, Chanock, Stephen J., Wang, Zhaoming, Skibola, Christine F., Melbye, Mads, Jayne, Sandrine, Catovsky, Daniel, Pepper, Chris, Zhang, Yawei, Miligi, Lucia, Sava, Georgina P., Monnereau, Alain, Martin-Garcia, David, Pratt, Guy, Summerfield, Geoffrey, Lan, Qing, Maynadie, Marc, Vajdic, Claire M., Dyer, Martin J. S., Goldin, Lynn R., Allsup, David J., Bea, Silvia, Majid, Aneela, Link, Brian K., Camp, Nicola J., Hall, Andrew G., Nieters, Alexandra, Ferri, Giovanni M., Law, Philip J., Rosenquist, Richard, Fraumeni, Joseph F., Jackson, Graham H., Curtin, Karen, Allan, James M., Offit, Kenneth, Cocco, Pierluigi, Southey, Melissa C., Sunter, Nicola J., Birmann, Brenda M., Morton, Lindsay M., Smedby, Karin E., Topka, Sabine, Pettitt, Andrew R., Benavente, Yolanda, Zheng, Tongzhang, Severson, Richard K., Vermeulen, Roel C. H., Cozen, Wendy, Holroyd, Amy, Riboli, Elio, Ennas, Maria Grazia, Albanes, Demetrius, Brooks-Wilson, Angela R., Carracedo, Angel, Fegan, Chris, Glenn, Martha, Spinelli, John J., Call, Timothy G., Diver, W Ryan, Liebow, Mark, Purdue, Mark P., North, Kari E., Speedy, Helen E., Joseph, Vijai, Brennan, Paul, Cerhan, James R., Tinker, Lesley F., Dearden, Claire, and Mainou-Fowler, Tryfonia
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3. Good health - Abstract
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
44. Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma.
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Shuhua Yi, Yuting Yan, Meiling Jin, Bhattacharya, Supriyo, Yi Wang, Yiming Wu, Lu Yang, Gine, Eva, Clot, Guillem, Lu Chen, Ying Yu, Dehui Zou, Jun Wang, An T. Phan, Rui Cui, Fei Li, Qi Sun, Qiongli Zhai, Tingyu Wang, and Zhen Yu
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- *
MANTLE cell lymphoma , *B cell receptors , *TRANSCRIPTOMES , *GENETIC mutation , *DNA repair , *CLINICAL indications , *PROTEINS , *SURVIVAL , *RESEARCH , *RESEARCH methodology , *PROGNOSIS , *EVALUATION research , *COMPARATIVE studies , *GENE expression profiling , *GENES , *RESEARCH funding , *NON-Hodgkin's lymphoma - Abstract
Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed a comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal samples from 16 patients and matched RNA-Seq data from 48 samples. We classified MCL into 4 robust clusters (C1-C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation, amp(11q13), and active B cell receptor (BCR) signaling. C2 was enriched with del(11q)/ATM mutations and upregulation of NF-κB and DNA repair pathways. C3 was characterized by mutations in SP140, NOTCH1, and NSD2, with downregulation of BCR signaling and MYC targets. C4 harbored del(17p)/TP53 mutations, del(13q), and del(9p), and active MYC pathway and hyperproliferation signatures. Patients in these 4 clusters had distinct outcomes (5-year overall survival [OS] rates for C1-C4 were 100%, 56.7%, 48.7%, and 14.2%, respectively). We also inferred the temporal order of genetic events and studied clonal evolution of 16 patients before treatment and at progression/relapse. Eleven of these samples showed drastic clonal evolution that was associated with inferior survival, while the other samples showed modest or no evolution. Our study thus identifies genetic subsets that clinically define this malignancy and delineates clonal evolution patterns and their impact on clinical outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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45. Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage.
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Queirós, Ana C., Beekman, Renée, Vilarrasa-Blasi, Roser, Duran-Ferrer, Martí, Clot, Guillem, Merkel, Angelika, Raineri, Emanuele, Russiñol, Nuria, Castellano, Giancarlo, Beà, Sílvia, Navarro, Alba, Kulis, Marta, Verdaguer-Dot, Núria, Jares, Pedro, Enjuanes, Anna, Calasanz, María José, Bergmann, Anke, Vater, Inga, Salaverría, Itziar, and van de Werken, Harmen J.G.
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- *
B cell lymphoma , *DNA methylation , *MANTLE cell lymphoma , *EPIGENOMICS , *PRIMARY care - Abstract
Summary We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11 . Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome. [ABSTRACT FROM AUTHOR]
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- 2016
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46. CCND2 rearrangements are the most frequent genetic events in cydlin D1-mantle cell lymphoma.
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Salaverria, Itziar, Royo, Cristina, Carvajal-Cuenca, Alejandra, Clot, Guillem, Navarro, Alba, Valera, Alejandra, Song, Joo Y., Woroniecka, Renata, Rymkiewicz, Grzegorz, Klapper, Wolfram, Hartmann, Elena M., Sujobert, Pierre, Wlodarska, Iwona, Ferry, Judith A., Gaulard, Philippe, Ott, German, Rosenwald, Andreas, Lopez-Guillermo, Armando, Quintanilla-Martinez, Leticia, and Harris, Nancy L.
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CYCLINS , *LYMPHOMAS , *BIOMARKERS , *IMMUNOGLOBULIN genes , *PHOSPHORYLATION - Abstract
Cyclin D1-negative mantle cell lymphomas (MCL) are not well characterized, in part due to the difficulties in their recognition. SOX11 has been recently identified as a reliable biomarker of MCL, also expressed in the cyclin D1- variant. We investigated 40 lymphomas with MCL morphology and immunophenotype, negative for cyclin D1 expression/t(11;14)(q13;q32) but SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and had a poor outcome (5-year overall survival 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18/22 cases, in particular with light chains (10 IGK@, 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2 and CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1-SOX11+ MCL analyzed by copy number arrays were similar to the conventional cyclin D1+/SOX11+ MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome to the patients. This comprehensive characterization of a large series of cyclin D1- MCL indicates that these tumors are clinically and biologically similar to the conventional cyclin D1+ MCL and provides a basis for the proper identification and clinical management of these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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47. Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL.
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Rivas-Delgado A, López C, Clot G, Nadeu F, Grau M, Frigola G, Bosch-Schips J, Radke J, Ishaque N, Alcoceba M, Tapia G, Luizaga L, Barcena C, Kelleher N, Villamor N, Baumann T, Muntañola A, Sancho-Cia JM, García-Sancho AM, Gonzalez-Barca E, Matutes E, Brito JA, Karube K, Salaverria I, Enjuanes A, Wiemann S, Heppner FL, Siebert R, Climent F, Campo E, Giné E, López-Guillermo A, and Beà S
- Abstract
Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations ( p < 0.04) but more somatic variants ( p < 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 ( BCL2 ) gains and 6q and 9p21.3 ( CDKN2A/B ) deletions. PIM1 , MYD88
L265P , CD79B , TBL1XR1 , MEF2B , CIITA , EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches., Competing Interests: Ferran Nadeu has received honoraria from Janssen, AbbVie, AstraZeneca, and SOPHiA GENETICS for speaking at educational activities; has received research support from Gilead; and has licensed the use of the protected IgCaller algorithm to Diagnóstica Longwood. Tycho Baumann has received consulting fees or honoraria from Janssen, Roche, Novartis, Merck, Gilead/Kite, Incyte, Lilly, Abbvie, AstraZeneca, and BeiGene. Alejandro Martin García‐Sancho has received consulting fees or honoraria from Janssen, Roche, BMS/Celgene, Kyowa Kirin, Clinigen, EUSAPharma, Novartis, Gilead/Kite, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Ideogen, Abbvie, and BeiGene. Elías Campo has been a consultant for GenMab, and Takeda; has received research support from AstraZeneca; received honoraria from Janssen, EUSPharma, Takeda, and Roche for speaking at educational activities; and is an inventor on a Lymphoma and Leukemia Molecular Profiling Project patent “Method for subtyping lymphoma subtypes by means of expression profiling” (PCT/US2014/64161) and a bioinformatic tool (IgCaller) licensed to Diagnostic Longwood. Eva Giné has received honoraria or consulting fees from Gilead, Kite Pharma, Janssen, Genmab, Miltenyi, and Lilly; has received research support from Janssen and travel expenses from Gilead and Kite Pharma. Armando López Guillermo served on the advisory board of Roche, Celgene, Novartis, and Gilead/Kite, received grants from Celgene and Gilead/Kite, and travel expenses from Kite/Gilead. The remaining authors declare no competing interests., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)- Published
- 2024
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48. Feasibility and Impact of Embedding an Extended DNA and RNA Tissue-Based Sequencing Panel for the Routine Care of Patients with Advanced Melanoma in Spain.
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Castrejon N, Martin R, Carrasco A, Castillo P, Garcia A, Albero-González R, García M, Marginet M, Palau N, Hernández M, Montironi C, Clot G, Arance A, Alos L, and Teixido C
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- Humans, Male, Female, Middle Aged, Aged, Spain, Adult, High-Throughput Nucleotide Sequencing methods, Aged, 80 and over, Feasibility Studies, Proto-Oncogene Proteins B-raf genetics, Biomarkers, Tumor genetics, Skin Neoplasms genetics, Skin Neoplasms pathology, Melanoma genetics, Melanoma pathology, Melanoma therapy, Mutation
- Abstract
Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK , KIT , and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT , CTNNB1 , EGFR , ALK , HRAS , or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy., Competing Interests: C.T. declared no competing non-financial interests but reported advisory and consulting fees from Merck Sharp and Dohme (MSD), Novartis, and AstraZeneca, lecture fees from Roche, Pfizer, Biocartis, and MSD, and research from Novartis and AstraZeneca. Other authors declare no conflicts of interest.
- Published
- 2024
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49. Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma.
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Yi S, Yan Y, Jin M, Bhattacharya S, Wang Y, Wu Y, Yang L, Gine E, Clot G, Chen L, Yu Y, Zou D, Wang J, Phan AT, Cui R, Li F, Sun Q, Zhai Q, Wang T, Yu Z, Liu L, Liu W, Lyv R, Sui W, Huang W, Xiong W, Wang H, Li C, Xiao Z, Hao M, Wang J, Cheng T, Bea S, Herrera AF, Danilov A, Campo E, Ngo VN, Qiu L, and Wang L
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- Humans, Male, Female, Gene Expression Regulation, Neoplastic, Aged, Genomics, Middle Aged, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell pathology, Lymphoma, Mantle-Cell metabolism, Transcriptome, Gene Expression Profiling
- Published
- 2024
- Full Text
- View/download PDF
50. BCL3 rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases.
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Carbo-Meix A, Guijarro F, Wang L, Grau M, Royo R, Frigola G, Playa-Albinyana H, Buhler MM, Clot G, Duran-Ferrer M, Lu J, Granada I, Baptista MJ, Navarro JT, Espinet B, Puiggros A, Tapia G, Bandiera L, De Canal G, Bonoldi E, Climent F, Ribera-Cortada I, Fernandez-Caballero M, De la Banda E, Do Nascimento J, Pineda A, Vela D, Rozman M, Aymerich M, Syrykh C, Brousset P, Perera M, Yanez L, Ortin JX, Tuset E, Zenz T, Cook JR, Swerdlow SH, Martin-Subero JI, Colomer D, Matutes E, Bea S, Costa D, Nadeu F, and Campo E
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- Humans, In Situ Hybridization, Fluorescence, Translocation, Genetic, Gene Rearrangement, Immunoglobulin Heavy Chains genetics, Chromosomes, Human, Pair 14 genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Lymphoma, Large B-Cell, Diffuse genetics
- Abstract
The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively.
- Published
- 2024
- Full Text
- View/download PDF
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