title: A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling.
abstract: BACKGROUND
  The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is unclear. We used transcriptional and genomic profiling to define Burkitt's lymphoma more precisely and to distinguish subgroups in other types of mature aggressive B-cell lymphomas.
  
  
  METHODS
  We performed gene-expression profiling using Affymetrix U133A GeneChips with RNA from 220 mature aggressive B-cell lymphomas, including a core group of 8 Burkitt's lymphomas that met all World Health Organization (WHO) criteria. A molecular signature for Burkitt's lymphoma was generated, and chromosomal abnormalities were detected with interphase fluorescence in situ hybridization and array-based comparative genomic hybridization.
  
  
  RESULTS
  We used the molecular signature for Burkitt's lymphoma to identify 44 cases: 11 had the morphologic features of diffuse large-B-cell lymphomas, 4 were unclassifiable mature aggressive B-cell lymphomas, and 29 had a classic or atypical Burkitt's morphologic appearance. Also, five did not have a detectable IG-myc Burkitt's translocation, whereas the others contained an IG-myc fusion, mostly in simple karyotypes. Of the 176 lymphomas without the molecular signature for Burkitt's lymphoma, 155 were diffuse large-B-cell lymphomas. Of these 155 cases, 21 percent had a chromosomal breakpoint at the myc locus associated with complex chromosomal changes and an unfavorable clinical course.
  
  
  CONCLUSIONS
  Our molecular definition of Burkitt's lymphoma clarifies and extends the spectrum of the WHO criteria for Burkitt's lymphoma. In mature aggressive B-cell lymphomas without a gene signature for Burkitt's lymphoma, chromosomal breakpoints at the myc locus were associated with an adverse clinical outcome.
authors.affiliation: Institute of Pathology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.forename: Hilmar
authors.initials: H
authors.lastname: Berger
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Swen
authors.initials: S
authors.lastname: Wessendorf
authors.forename: Thomas F E
authors.initials: TF
authors.lastname: Barth
authors.forename: Heinz-Wolfram
authors.initials: HW
authors.lastname: Bernd
authors.forename: Sergio B
authors.initials: SB
authors.lastname: Cogliatti
authors.forename: Judith
authors.initials: J
authors.lastname: Dierlamm
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Eugenia
authors.initials: E
authors.lastname: Haralambieva
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Dirk
authors.initials: D
authors.lastname: Hasenclever
authors.forename: Michael
authors.initials: M
authors.lastname: Kühn
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Hans-Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Reza M
authors.initials: RM
authors.lastname: Parwaresch
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Maciej
authors.initials: M
authors.lastname: Rosolowski
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwaenen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stürzenhofecker
authors.forename: Monika
authors.initials: M
authors.lastname: Szczepanowski
authors.forename: Heiko
authors.initials: H
authors.lastname: Trautmann
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Wacker
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000465:Algorithms; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D020869:Gene Expression Profiling; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis; D015996:Survival Rate; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm