Molecular characterization of diffuse large B-cell lymphomas associated with hepatitis C virus infection.

Autor: Sciarra R; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Merli M; Division of Hematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy., Cristinelli C; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Lucioni M; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Anatomic Pathology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Zibellini S; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Riboni R; Anatomic Pathology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Furlan D; Anatomic Pathology Unit, University of Insubria, Ospedale di Circolo, Varese, Italy., Uccella S; Department of Biomedical Sciences, Humanitas University, Milan, Italy.; Pathology Service, IRCCS, Humanitas Research Hospital, Milan, Italy., Zerbi C; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Bianchi B; Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi-ASST Sette Laghi, Varese, Italy., Gotti M; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Ferretti VV; Biostatistics and Clinical Trial Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Varraso C; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Fraticelli S; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Anatomic Pathology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Lazic T; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Defrancesco I; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Medical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy., Mora B; Division of Hematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy., Libera L; Anatomic Pathology Unit, University of Insubria, Ospedale di Circolo, Varese, Italy., Mazzacane A; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Carpi F; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Berliner M; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Neri G; Department of Molecular Medicine, University of Pavia, Pavia, Italy., Rizzo E; enGenome s.r.l., Pavia, Italy., De Paoli F; enGenome s.r.l., Pavia, Italy., Sessa F; Anatomic Pathology Unit, University of Insubria, Ospedale di Circolo, Varese, Italy., Passamonti F; Division of Hematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.; University of Milan, Milan, Italy., Paulli M; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Anatomic Pathology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Arcaini L; Department of Molecular Medicine, University of Pavia, Pavia, Italy.; Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Jun; Vol. 204 (6), pp. 2242-2253. Date of Electronic Publication: 2024 Mar 05.
DOI: 10.1111/bjh.19378
Abstrakt: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphoma (DLBCL) displays peculiar clinicopathological characteristics, but its molecular landscape is not fully elucidated. In this study, we investigated the clinicopathological and molecular features of 54 patients with HCV-associated DLBCL. The median age was 71 years. An underlying marginal zone lymphoma component was detected in 14.8% of cases. FISH analysis showed rearrangements involving BCL6 in 50.9% of cases, MYC in 11.3% and BCL2 in 3.7%. Lymph2Cx-based assay was successful in 38 cases, recognizing 16 cases (42.1%) as ABC and 16 cases as GCB subtypes, while six resulted unclassified. ABC cases exhibited a higher lymphoma-related mortality (LRM). Next-generation sequencing analysis showed mutations in 158/184 evaluated genes. The most frequently mutated genes were KMT2D (42.6%), SETD1B (33.3%), RERE (29.4%), FAS and PIM1 (27.8%) and TBL1XR1 (25.9%). A mutation in the NOTCH pathway was detected in 25.9% of cases and was associated with worst LRM. Cluster analysis by LymphGen classified 29/54 cases within definite groups, including BN2 in 14 (48.2%), ST2 in seven (24.2%) and MCD and EZB in four each (13.8%). Overall, these results indicate a preferential marginal zone origin for a consistent subgroup of HCV-associated DLBCL cases and suggest potential implications for molecularly targeted therapies.
(© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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