Variation in gene expression patterns in follicular lymphoma and the response to rituximab

Abstract

Analysis of the patterns of gene expression in follicular lymphomas from 24 patients suggested that two groups of tumors might be distinguished. All patients, whose biopsies were obtained before any treatment, were treated with rituximab, a monoclonal antibody directed against the B cell antigen, CD20. Gene expression patterns in the tumors that subsequently failed to respond to rituximab appeared more similar to those of normal lymphoid tissues than to gene expression patterns of tumors from rituximab responders. These findings suggest the possibility that the response of follicular lymphoma to rituximab treatment may be predicted from the gene expression pattern of tumors.

Figure 1

Hierarchical cluster analysis of gene expression patterns in follicular lymphoma. (A) Patterns of gene expression in FL lymph nodes from rituximab responders cluster with normal lymphoid tissue. A total of 20 FL lymph node samples from 16 patients and four normal lymphoid tissues (two tonsil and two spleen) from four different patients were sorted by hierarchical clustering based on similarity of gene expression. The resulting dendrogram is shown. Patient pathological diagnosis or normal tissue type, and response to rituximab treatment are shown. Samples are color coded by response to rituximab (for FL samples) or normal tissue for simplicity. For four patients, paired samples are presented; biopsy samples obtained later are identified by patient number plus “.2”. In three cases (patients 6, 8, and 18), paired samples clustered together (black bars). The two samples from patient 13 clustered on separate branches of the dendrogram (arrows). (B) Patterns of gene expression in FL samples and normal lymphoid tissue. Hierarchical clustering of genes and samples was performed. Variation of gene expression measured with 2,037 genes in 20 FL and four nonmalignant lymphoid tissue samples. Data are presented in a matrix format; each row represents a particular cDNA and each column is an individual FL or normal lymphoid tissue sample. For each sample, the ratio of the abundance of the mRNA measured by each cDNA clone to the median abundance of the mRNA across all tissue samples is represented by color in the corresponding cell in the matrix. Green represents transcript levels less than the median, black represents transcript levels equal to the median, and red represents transcript levels greater than the median. Color saturation represents the magnitude of the ratio relative to the median for each cell (see scale). Colored bars the to right of the matrix define groups of genes with similar expression patterns in normal lymphoid tissues, with blue denoting genes displaying relatively higher expression in spleen, purple denoting genes with higher expression in tonsil, and brown denoting genes with lower expression in spleen. Data can be viewed on our web site at http://genome-www.stanford.edu/rituximab/.