Heterogeneous gene-expression changes accompany histological and clinical transformation of FL. (A) Number of transformed FL cases demonstrating at least 3-fold up- or down-regulation of identical unique named genes. The majority of genes demonstrated similar changes in four or less transformed specimens, thus further emphasizing the marked genetic heterogeneity of the transformation process. (B) Hierarchical clustering of the 671 unique genes and 12 transformed FL specimen pairs (type 1 experiments). Two expression profiles each accounting for half of the transformed pairs are disclosed. Expression of these 671 genes was either up- or down-regulated on transformation and none of the genes demonstrated a uniform change in the same direction in the majority of tested tumor pairs. The results of the repeated analyses of case IL124 were averaged and presented as a single value and are marked by *. The ratios are a measure of relative gene expression in each experimental sample and were depicted according to the color scale shown at the bottom. As indicated, the scale extends from fluorescence ratios of 0.25–4 (−2 to + 2 in log base 2 units). Gray indicates missing or excluded data. (C) Hierarchical clustering of the 91 human genes reported as regulated by c-myc and 12 transformed FL specimen pairs. Stratification of the specimen pairs into two major divisions similar to those observed in B.

Gene-expression clusters in post-transformation and de novo DLBCL. Depicted are 2,205 gene-expression measurements made on 27 microarray analyses of 12 post-transformation DLBCL, 11 de novo DLBCL, cell lines, and purified germinal center B (GCB) cells. Each row represents a separate cDNA clone on the microarray and each column a separate mRNA sample. The results presented represent the ratio of hybridization of fluorescent cDNA probes prepared from each experimental mRNA sample to a reference mRNA sample, relative gene expression, depicted according to the color scale shown in Fig. . A, ABC type DLBCL; G, GCB type DLBCL [as determined previously for these cases ()].

Mean relative expression of genes comprising the “CD20” and the “CD52W” clusters and of the HLA-E gene in FL diagnosis, transformed, and de novo DLBCL specimens. Mean relative expression was calculated from the sum of expression of each gene in the cluster divided by the number of genes in the cluster. Results from different specimens from the same patient are marked by the same color. All of the results in de novo DLBCL are in gray.