The notch pathway is recurrently mutated in diffuse large B-Cell lymphoma associated with hepatitis c virus infection

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 GuerreraRoberta Sciarra, Gianluca Gaidano, Mario Cazzola, Marco Paulli

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatitis C virus has been found to be associated with B-cell non-Hodgkin lymphomas, mostly marginal zone lym-phomas 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 lym-phoma. 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. NOTCH2 mutations were detected in 9 of 46 (20%) hepatitis C virus-positive patients, and NOTCH1 mutations in 2 of 46 (4%). By contrast, only one of 64 HCV-negative patients had a NOTCH1 or NOTCH2 mutation. The frequency of the NOTCH pathway lesions was significantly higher in hepatitis C virus-positive patients (P=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 versus 62% (95%CI: 42%-77%) for those without these genetic lesions. By uni-variate analysis, age over 60 years, NOTCH2 mutation, and any mutation of the NOTCH pathway (NOTCH2, NOTCH1, SPEN) were associated with shorter overall survival. Mutation of the NOTCH pathway retained an independent significance (P=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.

Original languageEnglish
Pages (from-to)246-252
Number of pages7
JournalHaematologica
Volume100
Issue number2
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'The notch pathway is recurrently mutated in diffuse large B-Cell lymphoma associated with hepatitis c virus infection'. Together they form a unique fingerprint.

Cite this