Sandeep S. Dave, M.D., Kai Fu, M.D., Ph.D., George W. Wright, Ph.D., Lloyd T. Lam, Ph.D., Philip Kluin, M.D., Evert-Jan Boerma, B.S., Timothy C. Greiner, M.D., Dennis D. Weisenburger, M.D., Andreas Rosenwald, M.D., German Ott, M.D., Hans-Konrad Müller-Hermelink, M.D., Randy D. Gascoyne, M.D., Jan Delabie, M.D., Lisa M. Rimsza, M.D., Rita M. Braziel, M.D., Thomas M. Grogan, M.D., Elias Campo, M.D., Elaine S. Jaffe, M.D., Bhavana J. Dave, Ph.D., Warren Sanger, Ph.D., Martin Bast, B.S., Julie M. Vose, M.D., James O. Armitage, M.D., Joseph M. Connors, M.D., Erlend B. Smeland, M.D., Ph.D., Stein Kvaloy, M.D., Ph.D., Harald Holte, M.D., Ph.D., Richard I. Fisher, M.D., Thomas P. Miller, M.D., Emilio Montserrat, M.D., Wyndham H. Wilson, M.D., Ph.D., Manisha Bahl, B.S., Hong Zhao, M.S., Liming Yang, Ph.D., John Powell, M.S., Richard Simon, D.Sc., Wing C. Chan, M.D., Louis M. Staudt, M.D., Ph.D., for the Lymphoma/Leukemia Molecular Profiling Project
Background The distinction between Burkitt's lymphoma and diffuselarge-B-cell lymphoma is crucial because these two types oflymphoma require different treatments. We examined whether gene-expressionprofiling could reliably distinguish Burkitt's lymphoma fromdiffuse large-B-cell lymphoma.
Methods Tumor-biopsy specimens from 303 patients with aggressivelymphomas were profiled for gene expression and were also classifiedaccording to morphology, immunohistochemistry, and detectionof the t(8;14) c-myc translocation.
Results A classifier based on gene expression correctly identifiedall 25 pathologically verified cases of classic Burkitt's lymphoma.Burkitt's lymphoma was readily distinguished from diffuse large-B-celllymphoma 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-complexclass I genes and nuclear factor-B target genes. Eight specimenswith a pathological diagnosis of diffuse large-B-cell lymphomahad the typical gene-expression profile of Burkitt's lymphoma,suggesting they represent cases of Burkitt's lymphoma that aredifficult to diagnose by current methods. Among 28 of the patientswith a molecular diagnosis of Burkitt's lymphoma, the overallsurvival was superior among those who had received intensivechemotherapy regimens instead of lower-dose regimens.
Conclusions Gene-expression profiling is an accurate, quantitativemethod for distinguishing Burkitt's lymphoma from diffuse large-B-celllymphoma.
Source Information
From the National Cancer Institute (S.S.D., G.W.W., L.T.L., E.S.J., W.H.W., M.B., H.Z., R.S., L.M.S.) and the Center for Information Technology (L.Y., J.P.), National Institutes of Health, Bethesda, Md.; University of Nebraska Medical Center, Omaha (K.F., T.C.G., D.D.W., B.J.D., W.S., M.B., J.M.V., J.O.A., W.C.C.); Groningen University Medical Center, University of Groningen, Groningen, the Netherlands (P.K., E.-J.B.); University of Würzburg, Würzburg, Germany (A.R., G.O., H.-K.M.-H.); British Columbia Cancer Agency, Vancouver, B.C., Canada (R.D.G., J.M.C.); Norwegian Radium Hospital, Norway Hospital Clinic, Oslo ( J.D., E.B.S., S.K., H.H.); Southwest Oncology Group (L.M.R., R.M.B., T.M.G., R.I.F., T.P.M.); University of Arizona Cancer Center, Tucson (L.M.R., T.M.G., T.P.M.); Oregon Health and Science University, Portland (R.M.B.); University of Barcelona, Barcelona (E.C., E.M.); University of Oslo, Oslo (E.B.S.); and James P. Wilmot Cancer Center, University of Rochester School of Medicine, Rochester, N.Y. (R.I.F.).
Address reprint requests to Dr. Staudt at the Metabolism Branch, CCR, NCI, Bldg. 10, Rm. 4N114, NIH, 9000 Rockville Pike, Bethesda, MD 20892, or at lstaudt{at}mail.nih.gov.
Genomic Diagnosis of Burkitt's Lymphoma
Lin B. T., Dave S. S., Staudt L. M., Hummel M., Stein H., Siebert R., the Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe
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N Engl J Med 2006;
355:1064-1065, Sep 7, 2006.
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