Microarray-based classification of diffuse large B-cell lymphoma.
OBJECTIVE
Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL.


RESULTS
First, three previously published gene lists were converted to the HG-U133A probe sets and used for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1 was only expressed in the ABC and in Type-3 samples. The 5-year survival was similar between the groups, but GCB patients showed a better initial response to CHOP or CHOP-like regimens than the remaining patients and tended to have less advanced disease and lower IPI scores. As a next step, an improved set of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004;103:1862-1868) to exhibit a higher specificity than the original gene lists.


CONCLUSIONS
We conclude that gene expression profiling with Affymetrix Genechips is efficient to distinguish between GCB and ABC types of DLBCL and that these are likely to represent separate biological entities. The Genechip platform is highly standardised and therefore useful for future prospective investigations to establish the value of gene expression profiling in the clinical management of DLBCL.
Poulsen
Christian Bjørn
CB
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Denmark. c.poulsen@rh.dk
Borup
Rehannah
R
Nielsen
Finn Cilius
FC
Borregaard
Niels
N
Hansen
Mads
M
Grønbaek
Kirsten
K
Møller
Michael Boe
MB
Ralfkiaer
Elisabeth
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D014178:Translocation, Genetic / Q000235:genetics
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D015260:Neprilysin