Epstein-Barr virus status of sporadic Burkitt lymphoma is associated with patient age and mutational features.

Abstract

Sporadic Burkitt lymphoma (BL) is the most frequent tumour of children and adolescents but a rare subtype of lymphomas in adults. To date most molecular data have been obtained from lymphomas arising in the young. Recently, Epstein-Barr virus (EBV) positive and negative BL in young patients was shown to differ in molecular features. In the present study, we present a large age-overarching cohort of sporadic BL (n = 162) analysed by immunohistochemistry, translocations of MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), B-cell leukaemia/lymphoma 2 (BCL2) and B-cell leukaemia/lymphoma 6 (BCL6) and by targeted sequencing. We illustrate an age-associated inter-tumoral molecular heterogeneity in this disease. Mutations affecting inhibitor of DNA binding 3, HLH protein (ID3), transcription factor 3 (TCF3) and cyclin D3 (CCND3), which are highly recurrent in paediatric BL, and expression of sex determining region Y-box transcription factor 11 (SOX11) declined with patient age at diagnosis (P = 0·0204 and P = 0·0197 respectively). In contrast, EBV was more frequently detected in adult patients (P = 0·0262). Irrespective of age, EBV-positive sporadic BL showed significantly less frequent mutations in ID3/TCF3/CCND3 (P = 0·0088) but more often mutations of G protein subunit alpha 13 (GNA13; P = 0·0368) and forkhead box O1 (FOXO1; P = 0·0044) compared to EBV-negative tumours. Our findings suggest that among sporadic BL an EBV-positive subgroup of lymphomas increases with patient age that shows distinct pathogenic features reminiscent of EBV-positive endemic BL.

• Authors: Julia Richter, Katharina John, Annette M Staiger, Andreas Rosenwald, Katrin Kurz, Ulf Michgehl, German Ott, Sören Franzenburg, Christian Kohler, Jasmin Finger, Ilske Oschlies, Ulrike Paul, Reiner Siebert, Rainer Spang, Birgit Burkhardt, Wolfram Klapper
• Journal: British journal of haematology (Br J Haematol) Vol. 196 Issue 3 Pg. 681-689 (02 2022) ISSN: 1365-2141 [Electronic] England
• PMID: 34617271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Tumor

Topics

• Adolescent
• Adult
• Age Factors
• Age of Onset
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Burkitt Lymphoma (diagnosis, epidemiology, etiology)
• Cell Transformation, Viral
• Child
• Child, Preschool
• DNA Mutational Analysis
• Disease Susceptibility
• Epstein-Barr Virus Infections (complications, virology)
• Female
• Gene Expression
• Gene Expression Profiling
• Genetic Predisposition to Disease
• Herpesvirus 4, Human (physiology)
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Mutation
• Young Adult