@article{Luca Arcaini_Davide Rossi_Marco Lucioni_Marta Nicola_Alessio Bruscaggin_Valeria Fiaccadori_Roberta Riboni_Antonio Ramponi_Virginia V. Ferretti_Stefania Cresta_Gloria Margiotta Casaluci_Maurizio Bonfichi_Manuel Gotti_Michele Merli_Aldo Maffi_Mariarosa Arra_Marzia Varettoni_Sara Rattotti_Lucia Morello_Maria Luisa Guerrera_Roberta Sciarra_Gianluca Gaidano_Mario Cazzola_Marco Paulli_2015, place={Pavia, Italy}, title={The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection}, volume={100}, url={https://haematologica.org/article/view/7283}, DOI={10.3324/haematol.2014.116855}, abstractNote={Hepatitis C virus has been found to be associated with B-cell non-Hodgkin lymphomas, mostly marginal zone lymphomas and diffuse large B-cell lymphoma. Deregulation of signaling pathways involved in normal marginal zone development (NOTCH pathway, NF-κB, and BCR signaling) has been demonstrated in splenic marginal zone lymphoma. We studied mutations of NOTCH pathway signaling in 46 patients with hepatitis C virus-positive diffuse large B-cell lymphoma and in 64 patients with diffuse large B-cell lymphoma unrelated to HCV. <em>NOTCH2</em> mutations were detected in 9 of 46 (20%) hepatitis C virus-positive patients, and <em>NOTCH1</em> mutations in 2 of 46 (4%). By contrast, only one of 64 HCV-negative patients had a <em>NOTCH1</em> or <em>NOTCH2</em> mutation. The frequency of the NOTCH pathway lesions was significantly higher in hepatitis C virus-positive patients (<em>P</em>=0.002). The 5-year overall survival was 27% (95%CI: 5%–56%) for hepatitis C virus-positive diffuse large B-cell lymphoma patients carrying a NOTCH pathway mutation <em>versus</em> 62% (95%CI: 42%–77%) for those without these genetic lesions. By univariate analysis, age over 60 years, <em>NOTCH2</em> mutation, and any mutation of the NOTCH pathway (<em>NOTCH2, NOTCH1, SPEN</em>) were associated with shorter overall survival. Mutation of the NOTCH pathway retained an independent significance (<em>P</em&gt;=0.029). In conclusion, a subset of patients with hepatitis C virus-positive diffuse large B-cell lymphoma displays a molecular signature of splenic marginal zone and has a worse clinical outcome.}, number={2}, journal={Haematologica}, author={Luca Arcaini and Davide Rossi and Marco Lucioni and Marta Nicola and Alessio Bruscaggin and Valeria Fiaccadori and Roberta Riboni and Antonio Ramponi and Virginia V. Ferretti and Stefania Cresta and Gloria Margiotta Casaluci and Maurizio Bonfichi and Manuel Gotti and Michele Merli and Aldo Maffi and Mariarosa Arra and Marzia Varettoni and Sara Rattotti and Lucia Morello and Maria Luisa Guerrera and Roberta Sciarra and Gianluca Gaidano and Mario Cazzola and Marco Paulli}, year={2015}, month={Jan.}, pages={246-252} }