title: Germ cell and tumor associated piRNAs in the medaka and Xiphophorus melanoma models.
abstract: A growing number of studies report an abnormal expression of Piwi-interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution. However, little is known about piRNAs in somatic and neoplastic tissues of fish.
  
  
  
  To identify piRNA clusters that might be involved in melanoma pathogenesis, we use several transgenic lines of medaka, and platyfish/swordtail hybrids, which develop various types of melanoma. In these tumors Piwi, is expressed at different levels, depending on tumor type. To quantify piRNA levels, whole piRNA populations of testes and melanomas of different histotypes were sequenced. Because no reference piRNA cluster set for medaka or Xiphophorus was yet available we developed a software pipeline to detect piRNA clusters in our samples and clusters were selected that were enriched in one or more samples. We found several loci to be overexpressed or down-regulated in different melanoma subtypes as compared to hyperpigmented skin. Furthermore, cluster analysis revealed a clear distinction between testes, low-grade and high-grade malignant melanoma in medaka.
  
  
  
  Our data imply that dysregulation of piRNA expression may be associated with development of melanoma. Our results also reinforce the importance of fish as a suitable model system to study the role of piRNAs in tumorigenesis.
authors.affiliation: Physiological Chemistry I, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany. Susanne.kneitz@uni-wuerzburg.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.affiliation: Physiological Chemistry I, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
authors.forename: Rasmi R
authors.initials: RR
authors.lastname: Mishra
authors.affiliation: Department of Genetics, University of Georgia, Athens, USA.
authors.forename: Domitille
authors.initials: D
authors.lastname: Chalopin
authors.affiliation: Institute of Neuroscience, University of Oregon, 1425 E. 13th Avenue, Eugene, OR, 97403, USA.
authors.forename: John
authors.initials: J
authors.lastname: Postlethwait
authors.affiliation: Genome Sequencing Center, Washington University School of Medicine, 4444 Forest Park Blvd., St Louis, MO, 63108, USA.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Warren
authors.affiliation: The Xiphophorus Genetic Stock Center, Department of Chemistry and Biochemistry, 419 Centennial Hall, Texas State University, 601 University Drive, San Marcos, TX, 78666, USA.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Walter
authors.affiliation: Physiological Chemistry I, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.|Comprehensive Cancer Center Mainfranken, University Clinic Würzburg, Josef Schneider Straße 6, D-97074, Würzburg, Germany.|Texas Institute for Advanced Study and Department of Biology, Texas A&M University, College Station, Texas, 77843, USA.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schartl
mesh_terms: D000818:Animals; D001482:Base Composition; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003532:Cyprinodontiformes; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D056726:Genetic Association Studies; D005854:Germ Cells / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics*; D005810:Multigene Family; D009990:Oryzias; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D034741:RNA, Small Interfering
keywords: Fish model; Melanoma; Small RNA-sequencing; piRNA