title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Amato
authors.affiliation: Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Francesco
authors.initials: F
authors.lastname: Abate
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Piccaluga
authors.affiliation: Roche Tissue Diagnostic & Sequencing, Roche Diagnostic S.P.A. Monza (MB), Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Iacono
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fallerini
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: De Falco
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Maria Raffaella
authors.initials: MR
authors.lastname: Ambrosio
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Vaselious
authors.initials: V
authors.lastname: Mourmouras
authors.affiliation: Lacor Hospital, Gulu, Uganda.
authors.forename: Martin
authors.initials: M
authors.lastname: Ogwang
authors.affiliation: Lacor Hospital, Gulu, Uganda.
authors.forename: Valeria
authors.initials: V
authors.lastname: Calbi
authors.affiliation: Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Roul
authors.initials: R
authors.lastname: Rabadan
authors.affiliation: Institut Fur Pathologie, Campus Benjamin Franklin, Charitè, Universitatsmedizin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy lorenzo.leoncini@dbm.unisi.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.affiliation: From the Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005803:Genes, Immunoglobulin; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C407909:TCF3 protein, human
keywords: BCR; Burkitt lymphoma; Clonality analysis; NGS