Clonality analysis of immunoglobulin gene rearrangement by next-generation sequencing in endemic burkitt lymphoma suggests antigen drive activation of bcr as opposed to sporadic burkitt lymphoma

Teresa Amato, Francesco Abate, Pierpaolo Piccaluga, Michele Iacono, Chiara Fallerini, Alessandra Renieri, Giulia De Falco, Maria Raffaella Ambrosio, Vaselious Mourmouras, Martin Ogwang, Valeria Calbi, Roul Rabadan, Michael Hummel, Stefano Pileri, Lorenzo Leoncini, Cristiana Bellan

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development.

Original languageEnglish
Pages (from-to)116-127
Number of pages12
JournalAmerican Journal of Clinical Pathology
Volume145
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • BCR
  • Burkitt lymphoma
  • Clonality analysis
  • NGS

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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