E2F and Myc-Induced Lymphoma Figure 7. Distinct forms of Em-myc lymphomas. (A) Unsupervised hierarchical clustering of E2f22/2 and E2f42/2 Em-myc lymphomas amongst E2F wild type Em-myc lymphomas. Dendrogram of tumor subsets and heat map of the expression pattern of 958 genes used for the clustering analysis. Genes with sufficient variation in their expression across wild type (n = 50 plus 8 duplicates), E2f22/2 (n = 11), and E2f42/2 (n = 12) tumors were used to identify subgroups of tumors by two-way clustering. The tree classifies the tumors according to similarity of gene expression and identifies two major tumor clusters. The associated time of onset is shown by a color map (red = early onset and blue = late onset). The E2f22/2 and E2f42/2 Em-myc lymphomas and their dissected tumor phenotypes (Standard, Atypical, and Late) are identified. (B) Pathway expression signatures that characterize the distinct forms of Em-myc lymphomas. E2F wild type lymphomas (n = 50), E2f22/2 lymphomas (n = 11), and E2f42/2 lymphomas (n = 12) were classified on the basis of Myc pathway activity, the expression of a group of germinal-center B-cell genes, the expression of major- histocompatibility-complex class I genes, and NF-KB pathway activity. The associated dissected tumor phenotypes (Standard, Atypical, or Late) for the E2f42/2 Em-myc lymphomas are indicated. doi:10.1371/journal.pgen.1000640.g007 PLoS Genetics | www.plosgenetics.org 11 September 2009 | Volume 5 | Issue 9 | e1000640