TY - JOUR
T1 - Gene expression profile of serial samples of transformed B-cell lymphomas
AU - De Vos, Sven
AU - Hofmann, Wolf Karsten
AU - Grogan, Thomas M.
AU - Krug, Utz
AU - Schrage, Mathew
AU - Miller, Thomas P.
AU - Braun, Jonathan G.
AU - Wachsman, William
AU - Koeffler, H. Phillip
AU - Said, Jonathan W.
N1 - Funding Information:
This work was supported in part by the Neil Ruzic Fund and the Lymphoma Research Foundation of America and National Institutes of Health Grant NIH-UOICA66533-02. SdV is a fellow of the UCLA Specialty Training and Advanced Research (S.T.A.R.) program, and WKH is a recipient of a scholarship (HO2207/1-1) from the Deutsche Forschungsge-meinschaft. HPK is a member of the Jonsson Comprehensive Cancer Center and holds the endowed Mark Goodson Chair of Oncology Research at Cedars-Sinai Medical Center/UCLA School of Medicine. Address reprint requests to: Dr. S. de Vos, Division of Hematology/Oncology, UCLA Medical Center, 650 Charles E. Young Drive S., 11-266 Factor Building, Los Angeles, CA 90095-1678. E-mail: devos@mednet.ucla.edu
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Follicular lymphoma (FL) is characterized by a continuous rate of relapse and transformation to a high-grade lymphoma, usually diffuse large B-cell lymphoma (DLBCL), associated with a dismal prognosis and a poor response to conventional chemotherapy. The progression of indolent to aggressive FL is accompanied by the successive accumulation of recurrent chromosomal defects, but the resultant alterations of gene expression are largely unknown. To expand the understanding of the pathogenesis of FL transformation, we initially performed oligonucleotide microarray analyses using Affymetrix HuFL chips on five cases with matched snap-frozen lymph nodes before and after transformation. Expression data were analyzed using the Affymetrix Microarray Suite 4.0 and Genespring 4.0. Thirty-six genes with increased expression and 66 genes with decreased expression associated with transformation were identified and functionally classified. The expression of differentially expressed genes was confirmed by real-time quantitative RT-PCR (QRT-PCR) using a total of seven matched pairs and an additional five FL and five unrelated DLBCL. In addition, selected genes were further analyzed by QRT-PCR or immunohistochemistry using a large, unrelated series of FL (grades 1 to 3) as well as transformed and de novo DLBCL (total of 51 samples). The microarray results correlated with the protein expression data obtained from samples at the time of initial diagnosis and transformation. Furthermore, the expression of 25 candidate genes was evaluated by QRT-PCR with a 78% confirmation rate. Some of the identified genes, such as nucleobindin, interferon regulatory factor 4, and tissue inhibitor of metalloproteinases 1, are already known to be associated with high-grade non-Hodgkin's lymphoma. Novel candidate genes with confirmed increased and decreased expression in transformed DLBCL include ABL2 and NEK2, and PDCD1 and VDUP1, respectively. In summary, this study shows that transformation of FL to DLBCL is associated with a distinct set of differentially expressed genes of potential functional importance.
AB - Follicular lymphoma (FL) is characterized by a continuous rate of relapse and transformation to a high-grade lymphoma, usually diffuse large B-cell lymphoma (DLBCL), associated with a dismal prognosis and a poor response to conventional chemotherapy. The progression of indolent to aggressive FL is accompanied by the successive accumulation of recurrent chromosomal defects, but the resultant alterations of gene expression are largely unknown. To expand the understanding of the pathogenesis of FL transformation, we initially performed oligonucleotide microarray analyses using Affymetrix HuFL chips on five cases with matched snap-frozen lymph nodes before and after transformation. Expression data were analyzed using the Affymetrix Microarray Suite 4.0 and Genespring 4.0. Thirty-six genes with increased expression and 66 genes with decreased expression associated with transformation were identified and functionally classified. The expression of differentially expressed genes was confirmed by real-time quantitative RT-PCR (QRT-PCR) using a total of seven matched pairs and an additional five FL and five unrelated DLBCL. In addition, selected genes were further analyzed by QRT-PCR or immunohistochemistry using a large, unrelated series of FL (grades 1 to 3) as well as transformed and de novo DLBCL (total of 51 samples). The microarray results correlated with the protein expression data obtained from samples at the time of initial diagnosis and transformation. Furthermore, the expression of 25 candidate genes was evaluated by QRT-PCR with a 78% confirmation rate. Some of the identified genes, such as nucleobindin, interferon regulatory factor 4, and tissue inhibitor of metalloproteinases 1, are already known to be associated with high-grade non-Hodgkin's lymphoma. Novel candidate genes with confirmed increased and decreased expression in transformed DLBCL include ABL2 and NEK2, and PDCD1 and VDUP1, respectively. In summary, this study shows that transformation of FL to DLBCL is associated with a distinct set of differentially expressed genes of potential functional importance.
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U2 - 10.1097/01.LAB.0000053913.85892.E9
DO - 10.1097/01.LAB.0000053913.85892.E9
M3 - Article
C2 - 12594241
AN - SCOPUS:0037324949
SN - 0023-6837
VL - 83
SP - 271
EP - 285
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 2
ER -