학술논문
Molecular characterization of diffuse large B‐cell lymphomas associated with hepatitis C virus infection.
Document Type
Article
Author
Sciarra, Roberta; Merli, Michele; Cristinelli, Caterina; Lucioni, Marco; Zibellini, Silvia; Riboni, Roberta; Furlan, Daniela; Uccella, Silvia; Zerbi, Caterina; Bianchi, Benedetta; Gotti, Manuel; Ferretti, Virginia Valeria; Varraso, Chiara; Fraticelli, Sara; Lazic, Tanja; Defrancesco, Irene; Mora, Barbara; Libera, Laura; Mazzacane, Alessandro; Carpi, Federico
Source
Subject
*HEPATITIS C
*DIFFUSE large B-cell lymphomas
*MUCOSA-associated lymphoid tissue lymphoma
*HEPATITIS C virus
*FLUORESCENCE in situ hybridization
*NUCLEOTIDE sequencing
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Language
ISSN
0007-1048
Abstract
Summary: 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. [ABSTRACT FROM AUTHOR]