Microarray gene expression analysis of fixed archival tissue permits molecular classification and identification of potential therapeutic targets in diffuse large B-cell lymphoma.
AuthorsLinton, Kim M
Pepper, Stuart D
Byers, Richard J
Chan, W J
Radford, John A
AffiliationThe University of Manchester, Manchester Cancer Research Centre, Manchester, United Kingdom. email@example.com
MetadataShow full item record
AbstractRefractory/relapsed diffuse large B-cell lymphoma (DLBCL) has a poor prognosis. Novel drugs targeting the constitutively activated NF-κB pathway characteristic of ABC-DLBCL are promising, but evaluation depends on accurate activated B cell-like (ABC)/germinal center B cell-like (GCB) molecular classification. This is traditionally performed on gene microarray expression profiles of fresh biopsies, which are not routinely collected, or by immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tissue, which lacks reproducibility and classification accuracy. We explored the possibility of using routine archival FFPE tissue for gene microarray applications. We examined Affymetrix HG U133 Plus 2.0 gene expression profiles from paired archival FFPE and fresh-frozen tissues of 40 ABC/GCB-classified DLBCL cases to compare classification accuracy and test the potential for this approach to aid the discovery of therapeutic targets and disease classifiers in DLBCL. Unsupervised hierarchical clustering of unselected present probe sets distinguished ABC/GCB in FFPE with remarkable accuracy, and a Bayesian classifier correctly assigned 32 of 36 cases with >90% probability. Enrichment for NF-κB genes was appropriately seen in ABC-DLBCL FFPE tissues. The top discriminatory genes expressed in FFPE separated cases with high statistical significance and contained novel biology with potential therapeutic insights, warranting further investigation. These results support a growing understanding that archival FFPE tissues can be used in microarray experiments aimed at molecular classification, prognostic biomarker discovery, and molecular exploration of rare diseases.
CitationMicroarray gene expression analysis of fixed archival tissue permits molecular classification and identification of potential therapeutic targets in diffuse large B-cell lymphoma., 14 (3):223-32 J Mol Diagn
JournalJournal of Molecular Diagnostics
- Accurate classification of diffuse large B-cell lymphoma into germinal center and activated B-cell subtypes using a nuclease protection assay on formalin-fixed, paraffin-embedded tissues.
- Authors: Rimsza LM, Wright G, Schwartz M, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Cook JR, Tubbs RR, Braziel RM, Delabie J, Miller TP, Staudt LM
- Issue date: 2011 Jun 1
- Diffuse large B-cell lymphoma: sub-classification by massive parallel quantitative RT-PCR.
- Authors: Xue X, Zeng N, Gao Z, Du MQ
- Issue date: 2015 Jan
- Quantitative nuclease protection assay in paraffin-embedded tissue replicates prognostic microarray gene expression in diffuse large-B-cell lymphoma.
- Authors: Roberts RA, Sabalos CM, LeBlanc ML, Martel RR, Frutiger YM, Unger JM, Botros IW, Rounseville MP, Seligmann BE, Miller TP, Grogan TM, Rimsza LM
- Issue date: 2007 Oct
- QuantiGene Plex Represents a Promising Diagnostic Tool for Cell-of-Origin Subtyping of Diffuse Large B-Cell Lymphoma.
- Authors: Hall JS, Usher S, Byers RJ, Higgins RC, Memon D, Radford JA, Linton KM
- Issue date: 2015 Jul
- Microarray-based classification of diffuse large B-cell lymphoma.
- Authors: Poulsen CB, Borup R, Nielsen FC, Borregaard N, Hansen M, Grønbaek K, Møller MB, Ralfkiaer E
- Issue date: 2005 Jun