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Blood, 23 July 2009, Vol. 114, No. 4, pp. 826-834.
Prepublished online as a Blood First Edition Paper on May 26, 2009; DOI 10.1182/blood-2009-01-198580.


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LYMPHOID NEOPLASIA

Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations

Ellen Leich1,*, Itziar Salaverria2,*, Silvia Bea2, Andreas Zettl1, George Wright3, Victor Moreno4, Randy D. Gascoyne5, Wing-Chung Chan6, Rita M. Braziel7, Lisa M. Rimsza8, Dennis D. Weisenburger6, Jan Delabie9, Elaine S. Jaffe10, Andrew Lister11, Jude Fitzgibbon11, Louis M. Staudt12, Elena M. Hartmann1, Hans-Konrad Mueller-Hermelink1, Elias Campo2,{dagger}, German Ott1,13,{dagger}, and Andreas Rosenwald1,{dagger}

1 Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany; 2 Department of Pathology, University of Barcelona, Hospital Clinic, Barcelona, Spain; 3 Biometric Research Branch, National Cancer Institute (NCI), Rockville, MD; 4 Biostatistics and Bioinformatics Unit, IDIBELL-Catalan Institute of Oncology, University of Barcelona, Barcelona, Spain; 5 British Columbia Cancer Agency, University of British Columbia, Vancouver, BC; 6 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha; 7 Southwest Oncology Group, Oregon Health & Science University, Portland; 8 Department of Pathology, University of Arizona, Tucson; 9 Division of Pathology, Norwegian Radium Hospital, Oslo, Norway; 10 Laboratory of Pathology, NCI, Bethesda, MD; 11 Cancer Research UK, St Bartholomew's Hospital, London, United Kingdom; 12 Metabolism Branch, NCI, Bethesda, MD; and 13 Institute of Clinical Pathology, Robert-Bosch-Krankenhaus and Institute of Clinical Pharmacology, Stuttgart, Germany

Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles showed an enrichment of germinal center B cell–associated signatures in t(14;18)-positive FL, whereas activated B cell–like, NF{kappa}B, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t(14;18)-negative FL.


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