title: Sequential karyotyping in Burkitt lymphoma reveals a linear clonal evolution with increase in karyotype complexity and a high frequency of recurrent secondary aberrations.
abstract: Typical Burkitt lymphoma is characterized by an IG-MYC translocation and overall low genomic complexity. Clinically, Burkitt lymphoma has a favourable prognosis with very few relapses. However, the few patients experiencing disease progression and/or relapse have a dismal outcome. Here we report cytogenetic findings of seven cases of Burkitt lymphoma in which sequential karyotyping was performed at time of diagnosis and/or disease progression/relapse(s). After case selection, karyotype re-review and additional molecular analyses were performed in six paediatric cases, treated in Berlin-Frankfurt-Münster-Non-Hodgkin lymphoma study group trials, and one additional adult patient. Moreover, we analysed 18 cases of Burkitt lymphoma from the Mitelman database in which sequential karyotyping was performed. Our findings show secondary karyotypes to have a significant increase in load of cytogenetic aberrations with a mean number of 2, 5 and 8 aberrations for primary, secondary and third investigations. Importantly, this increase in karyotype complexity seemed to result from recurrent secondary chromosomal changes involving mainly trisomy 21, gains of 1q and 7q, losses of 6q, 11q, 13q, and 17p. In addition, our findings indicate a linear clonal evolution to be the predominant manner of cytogenetic evolution. Our data may provide a biological framework for the dismal outcome of progressive and relapsing Burkitt lymphoma.
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.|Department of Pathology & Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.|Department of Haematology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Sietse M
authors.initials: SM
authors.lastname: Aukema
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Theil
authors.affiliation: Non-Hodgkin Lymphoma Berlin-Frankfurt-Münster Group Study Centre, Department of Paediatric Haematology and Oncology, Justus Liebig University, Gießen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Bauer
authors.affiliation: Institute of Pathology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Bradtke
authors.affiliation: Non-Hodgkin Lymphoma Berlin-Frankfurt-Münster Group Study Center, Department of Pediatric Haematology and Oncology, University Children's Hospital, Münster, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Burkhardt
authors.affiliation: Non-Hodgkin Lymphoma Berlin-Frankfurt-Münster Group Study Center, Department of Pediatric Haematology and Oncology, University Children's Hospital, Münster, Germany.
authors.forename: Bettina R
authors.initials: BR
authors.lastname: Bonn
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University, Kiel, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Claviez
authors.affiliation: Institute of Pathology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.affiliation: Non-Hodgkin Lymphoma Berlin-Frankfurt-Münster Group Study Center, Department of Pediatric Haematology and Oncology, University Children's Hospital, Münster, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Makarova
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Nagel
authors.affiliation: Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Ilske
authors.initials: I
authors.lastname: Oschlies
authors.affiliation: Second Medical Department, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.affiliation: Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.affiliation: Institute of Pathology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Traulsen
authors.affiliation: Department of Pathology & Medical Biology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kluin
authors.affiliation: Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Kiel, Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Murga Penas
mesh_terms: D000293:Adolescent; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D060965:Clonal Evolution / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D016259:Genes, myc; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008962:Models, Theoretical; D009364:Neoplasm Recurrence, Local; D013997:Time Factors; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains
keywords: Burkitt lymphoma; MYC; clonal evolution; progression; relapse