Molecular diagnosis of Burkitt's lymphoma.
BACKGROUND
The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.


METHODS
Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.


RESULTS
A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt's lymphoma, suggesting they represent cases of Burkitt's lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt's lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens.


CONCLUSIONS
Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt's lymphoma from diffuse large-B-cell lymphoma.
Dave
Sandeep S
SS
National Cancer Institute, National Institutes of Health, Bethesda, Md, USA.
Fu
Kai
K
Wright
George W
GW
Lam
Lloyd T
LT
Kluin
Philip
P
Boerma
Evert-Jan
EJ
Greiner
Timothy C
TC
Weisenburger
Dennis D
DD
Rosenwald
Andreas
A
Ott
German
G
Müller-Hermelink
Hans-Konrad
HK
Gascoyne
Randy D
RD
Delabie
Jan
J
Rimsza
Lisa M
LM
Braziel
Rita M
RM
Grogan
Thomas M
TM
Campo
Elias
E
Jaffe
Elaine S
ES
Dave
Bhavana J
BJ
Sanger
Warren
W
Bast
Martin
M
Vose
Julie M
JM
Armitage
James O
JO
Connors
Joseph M
JM
Smeland
Erlend B
EB
Kvaloy
Stein
S
Holte
Harald
H
Fisher
Richard I
RI
Miller
Thomas P
TP
Montserrat
Emilio
E
Wilson
Wyndham H
WH
Bahl
Manisha
M
Zhao
Hong
H
Yang
Liming
L
Powell
John
J
Simon
Richard
R
Chan
Wing C
WC
Staudt
Louis M
LM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001499:Bayes Theorem; D002051:Burkitt Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D020869:Gene Expression Profiling; D005805:Genes, MHC Class I; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D016328:NF-kappa B