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

Br J Haematol. 2022 Feb;196(3):681-689. doi: 10.1111/bjh.17874. Epub 2021 Oct 6.


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.

Keywords: Burkitt lymphoma; Epstein-Barr virus status; age; mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Burkitt Lymphoma / diagnosis
  • Burkitt Lymphoma / epidemiology*
  • Burkitt Lymphoma / etiology*
  • Cell Transformation, Viral
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Disease Susceptibility*
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / 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


  • Biomarkers, Tumor