title: Association of tumor and plasma microRNA expression with tumor monosomy-3 in patients with uveal melanoma.
abstract: BACKGROUND
  Epigenetic events mediated by methylation and histone modifications have been associated with the development of metastasis in patients with uveal melanoma. The role of epigenetic events mediated by microRNA (miR) is less clear. Tumor and plasma miR expression was examined in patients with primary uveal melanoma with tumor monosomy-3, a predictor of metastasis.
  
  
  RESULTS
  miR profiling of tumors by microarray found six miRs over-expressed and 19 under-expressed in 33 tumors with monosomy-3 compared to 22 without. None of the miRs differentially expressed in tumors with and without monosomy-3 was differentially expressed in tumors with and without tumor infiltrating lymphocytes. Tumors manifesting monosomy-3 were also characterized by higher levels of TARBP2 and DDX17 and by lower levels of XPO5 and HIWI, miR biogenesis factors. miR profiling of plasma by a quantitative nuclease protection assay found elevated levels of 11 miRs and reduction in four in patients with tumor monosomy-3. Only three miRs differentially expressed in the tumor arrays were detectable in plasma. miRs implicated in uveal melanoma development were not differentially expressed. Elevated plasma levels in patients with tumor monosomy-3 of miR-92b, identified in the tumor array, and of miR-199-5p and miR-223, identified in the plasma array, were confirmed by quantitative real-time polymerase chain reaction. Levels were also higher in patients compared to normal controls.
  
  
  CONCLUSIONS
  These results support a role for epigenetic mechanisms in the development of metastasis in patients with uveal melanoma and the analysis of miRs as biomarkers of metastatic risk. They also suggest that potentially useful blood miRs may be derived from the host response as well as the tumor.
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH USA ; Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Achberger
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Aldrich
authors.affiliation: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Crabb
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: Yogen
authors.initials: Y
authors.lastname: Saunthararajah
authors.affiliation: Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH USA.
authors.forename: Arun D
authors.initials: AD
authors.lastname: Singh
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics*; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D009006:Monosomy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014604:Uveal Neoplasms / Q000097:blood / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: D035683:MicroRNAs; C525067:MIR223, human; C541874:MIRN92 microRNA, human; C531408:mirn199 microRNA, human
keywords: Biomarkers; Prognosis; miR-199-5p; miR-223; miR-92b