PDF file - 274K, Table S1. SigClust classification of 56 Trp53 null mouse mammary tumors. Table S2 Genes in the 323-irradiated host signature Table S3 Genes of the 72-gene centroid Table S4 Gene clusters that are induced within the subgroups of Figure 4A. Table S5. Biological functions of 323-IHC genes Table S6 Gene lists for gene clusters in Figure 5A and 6C. Figure S1. The irradiated host signature detects radiation-preceded human cancers. Figure S2 (Goes with Figure 4)
ARTICLE ABSTRACT
Purpose: Ionizing radiation is a well-established carcinogen in rodent models and a risk factor associated with human cancer. We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53-null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts. We asked whether expression metaprofiles could discern radiation-preceded human cancer or be informative in sporadic breast cancers.Experimental Design: Affymetrix microarray gene expression data from 56 Trp53-null mammary tumors were used to define gene profiles and a centroid that discriminates tumors arising in irradiated hosts. These were applied to publicly available human cancer datasets.Results: Host irradiation induces a metaprofile consisting of gene modules representing stem cells, cell motility, macrophages, and autophagy. Human orthologs of the host irradiation metaprofile discriminated between radiation-preceded and sporadic human thyroid cancers. An irradiated host centroid was strongly associated with estrogen receptor–negative breast cancer. When applied to sporadic human breast cancers, the irradiated host metaprofile strongly associated with basal-like and claudin-low breast cancer intrinsic subtypes. Comparing host irradiation in the context of TGF-β levels showed that inflammation was robustly associated with claudin-low tumors.Conclusions: Detection of radiation-preceded human cancer by the irradiated host metaprofile raises possibilities of assessing human cancer etiology. Moreover, the association of the irradiated host metaprofiles with estrogen receptor–negative status and claudin-low subtype suggests that host processes similar to those induced by radiation underlie sporadic cancers. Clin Cancer Res; 19(6); 1353–62. ©2013 AACR.
