Gene expression profile of serial samples of transformed B-cell lymphomas

Sven De Vos, Wolf Karsten Hofmann, Thomas M. Grogan, Utz Krug, Mathew Schrage, Thomas P Miller, Jonathan G. Braun, William Wachsman, H. Phillip Koeffler, Jonathan W. Said

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)271-285
Number of pages15
JournalLaboratory Investigation
Volume83
Issue number2
StatePublished - Feb 1 2003

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B-Cell Lymphoma
Follicular Lymphoma
Transcriptome
Lymphoma, Large B-Cell, Diffuse
Genes
Non-Hodgkin's Lymphoma
Gene Expression
Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-1
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Lymph Nodes
Immunohistochemistry
Recurrence
Drug Therapy
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

De Vos, S., Hofmann, W. K., Grogan, T. M., Krug, U., Schrage, M., Miller, T. P., ... Said, J. W. (2003). Gene expression profile of serial samples of transformed B-cell lymphomas. Laboratory Investigation, 83(2), 271-285.

Gene expression profile of serial samples of transformed B-cell lymphomas. / De Vos, Sven; Hofmann, Wolf Karsten; Grogan, Thomas M.; Krug, Utz; Schrage, Mathew; Miller, Thomas P; Braun, Jonathan G.; Wachsman, William; Koeffler, H. Phillip; Said, Jonathan W.

In: Laboratory Investigation, Vol. 83, No. 2, 01.02.2003, p. 271-285.

Research output: Contribution to journalArticle

De Vos, S, Hofmann, WK, Grogan, TM, Krug, U, Schrage, M, Miller, TP, Braun, JG, Wachsman, W, Koeffler, HP & Said, JW 2003, 'Gene expression profile of serial samples of transformed B-cell lymphomas', Laboratory Investigation, vol. 83, no. 2, pp. 271-285.
De Vos S, Hofmann WK, Grogan TM, Krug U, Schrage M, Miller TP et al. Gene expression profile of serial samples of transformed B-cell lymphomas. Laboratory Investigation. 2003 Feb 1;83(2):271-285.
De Vos, Sven ; Hofmann, Wolf Karsten ; Grogan, Thomas M. ; Krug, Utz ; Schrage, Mathew ; Miller, Thomas P ; Braun, Jonathan G. ; Wachsman, William ; Koeffler, H. Phillip ; Said, Jonathan W. / Gene expression profile of serial samples of transformed B-cell lymphomas. In: Laboratory Investigation. 2003 ; Vol. 83, No. 2. pp. 271-285.
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