A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling.
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.
Hummel
Michael
M
Institute of Pathology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany.
Bentink
Stefan
S
Berger
Hilmar
H
Klapper
Wolfram
W
Wessendorf
Swen
S
Barth
Thomas F E
TF
Bernd
Heinz-Wolfram
HW
Cogliatti
Sergio B
SB
Dierlamm
Judith
J
Feller
Alfred C
AC
Hansmann
Martin-Leo
ML
Haralambieva
Eugenia
E
Harder
Lana
L
Hasenclever
Dirk
D
Kühn
Michael
M
Lenze
Dido
D
Lichter
Peter
P
Martin-Subero
Jose Ignacio
JI
Möller
Peter
P
Müller-Hermelink
Hans-Konrad
HK
Ott
German
G
Parwaresch
Reza M
RM
Pott
Christiane
C
Rosenwald
Andreas
A
Rosolowski
Maciej
M
Schwaenen
Carsten
C
Stürzenhofecker
Benjamin
B
Szczepanowski
Monika
M
Trautmann
Heiko
H
Wacker
Hans-Heinrich
HH
Spang
Rainer
R
Loeffler
Markus
M
Trümper
Lorenz
L
Stein
Harald
H
Siebert
Reiner
R
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
D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm