Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility

摘要: Background: Germline polymorphisms can influence gene expression networks in normal mammalian tissues and affect disease susceptibility. We others have shown that analysis of this genetic architecture identify single genes whole pathways complex traits, including inflammation cancer Whether germline variants tumors undergone somatic alterations, the extent to which these tumor progression, is unknown. Results: Using an integrated linkage genomic a mouse model skin produces both benign malignant carcinomas, we document major changes control during development resulting from cell selection, events, microenvironment. The number significant quantitative trait loci (eQTL) progressively reduced when compared skin. However, novel tumor-specific eQTL are detected for several associated with susceptibility, IL18 (Il18), Granzyme E (Gzme), Sprouty homolog 2 (Spry2), Mitogen-activated protein kinase 4 (Map2k4). Conclusions: conclude substantially altered tumors, host factors microenvironment, mitogen-activated (MAP) signaling,