title: Genetic differences between paediatric and adult Burkitt lymphomas.
abstract: Dysregulation of MYC is the genetic hallmark of Burkitt lymphoma (BL) but it is encountered in other aggressive mature B-cell lymphomas. MYC dysregulation needs other cooperating events for BL development. We aimed to characterize these events and assess the differences between adult and paediatric BLs that may explain the different outcomes in these two populations. We analysed patterns of genetic aberrations in a series of 24 BLs: 11 adults and 13 children. We looked for genomic imbalances (copy number variations), copy-neutral loss of heterozygosity (CN-LOH) and mutations in TP53, CDKN2A, ID3 (exon 1), TCF3 (exon17) and CCND3 (exon 6). Young patients displayed more frequent 13q31.3q32.1 amplification, 7q32q36 gain and 5q23.3 CN-LOH, while 17p13 and 18q21.3 CN-LOH were only detected in adult BLs. ID3 mutations were present in all adult samples, but only in 42% of childhood cases. CCND3 and ID3 double-hit mutations, as well as 18q21 CN-LOH, seemed to be associated with poorer outcome. For the first time, we report different genetic anomalies between adult and paediatric BLs, suggesting age-related heterogeneity in Burkitt lymphomagenesis. This may explain the poorer prognosis of adult BLs. Additional studies are needed to confirm these results in the setting of clinical trials.
authors.affiliation: Department of Haematology, Cliniques universitaires Saint-Luc - Université catholique de Louvain, Brussels, Belgium.
authors.forename: Violaine
authors.initials: V
authors.lastname: Havelange
authors.affiliation: Centre for Human Genetics, Cliniques universitaires Saint-Luc - Université catholique de Louvain, Brussels, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pepermans
authors.affiliation: Centre for Human Genetics, Cliniques universitaires Saint-Luc - Université catholique de Louvain, Brussels, Belgium.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Ameye
authors.affiliation: Department of Pathology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ivan
authors.initials: I
authors.lastname: Théate
authors.affiliation: Laboratoire central d'Hématologie, CHU Lyon-Sud, Pierre-Bénite, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Callet-Bauchu
authors.affiliation: Laboratoire de Cytogénétique, CHU Bretonneau, Tours, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Barin
authors.affiliation: Laboratoire de génétique oncologique, Centre Henri Becquerel, Rouen, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Penther
authors.affiliation: Laboratoire d'hématologie, CHU Bordeaux, Pessac, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.affiliation: Centrum voor menselijke erfelijkheid, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Michaux
authors.affiliation: Laboratoire de Cytogénétique, CHU Dijon, Dijon, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Mugneret
authors.affiliation: Génétique des hémopathies, Hôpital Purpan, Toulouse, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.affiliation: Anatomie et cytologie pathologiques, CHU Bicêtre -Assistance Publique-Hôpitaux de Paris, INSERM U802, Université Paris-Sud 11, Le Kremlin-Bicêtre, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Raphaël
authors.affiliation: Human Molecular Genetics (GEHU), de Duve Institute - Université catholique de Louvain, Brussels, Belgium.
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
authors.affiliation: Department of Haematology, Cliniques universitaires Saint-Luc - Université catholique de Louvain, Brussels, Belgium.|Human Molecular Genetics (GEHU), de Duve Institute - Université catholique de Louvain, Brussels, Belgium.
authors.forename: Hélène A
authors.initials: HA
authors.lastname: Poirel
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002051:Burkitt Lymphoma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Burkitt lymphoma; CCND3; ID3; SNP-array; childhood