title: Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.
abstract: Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL) network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo 0310, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo 0313, Norway; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Quigley
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Eve
authors.initials: E
authors.lastname: Kandyba
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Genome Institute of Singapore, 60 Biopolis Street, #02-01 Genome Building, Singapore 138672, Singapore.
authors.forename: Phillips
authors.initials: P
authors.lastname: Huang
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Halliwill
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, 22381 Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Sjölund
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 9(th) Floor, Ciudad Autónoma de Buenos Aires 1121, Argentina.
authors.forename: Facundo
authors.initials: F
authors.lastname: Pelorosso
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wong
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Hirst
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Reyno
authors.initials: R
authors.lastname: Delrosario
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: abalmain@cc.ucsf.edu.
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D015870:Gene Expression / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005854:Germ Cells / Q000502:physiology; D007249:Inflammation / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D011110:Polymorphism, Genetic / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*