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. 2024 Jun;204(6):2242-2253.
doi: 10.1111/bjh.19378. Epub 2024 Mar 5.

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

Roberta Sciarra  1   2 , Michele Merli  3 , Caterina Cristinelli  1 , Marco Lucioni  1   4 , Silvia Zibellini  2 , Roberta Riboni  4 , Daniela Furlan  5 , Silvia Uccella  6   7 , Caterina Zerbi  1   2 , Benedetta Bianchi  8 , Manuel Gotti  2 , Virginia Valeria Ferretti  9 , Chiara Varraso  2 , Sara Fraticelli  1   4 , Tanja Lazic  1 , Irene Defrancesco  2   10 , Barbara Mora  3 , Laura Libera  5 , Alessandro Mazzacane  1 , Federico Carpi  1 , Martha Berliner  1 , Giuseppe Neri  1 , Ettore Rizzo  11 , Federica De Paoli  11 , Fausto Sessa  5 , Francesco Passamonti  3   12 , Marco Paulli  1   4 , Luca Arcaini  1   2
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Free article

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

Roberta Sciarra et al. Br J Haematol. 2024 Jun.
Free article

Abstract

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.

Keywords: NGS; Nanostring; diffuse large B‐cell lymphoma; hepatitis C virus.

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References

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