title: Gene expression profiling of alveolar soft-part sarcoma (ASPS).
abstract: BACKGROUND
  Alveolar soft-part sarcoma (ASPS) is an extremely rare, highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study.
  
  
  METHODS
  For seven patients with confirmed primary or metastatic ASPS, RNA samples were isolated immediately following surgery, reverse transcribed to cDNA and each sample hybridized to duplicate high-density human U133 plus 2.0 microarrays. Array data was then analyzed relative to arrays hybridized to universal RNA to generate an unbiased transcriptome. Subsequent gene ontology analysis was used to identify transcripts with therapeutic or diagnostic potential. A subset of the most interesting genes was then validated using quantitative RT-PCR and immunohistochemistry.
  
  
  RESULTS
  Analysis of patient array data versus universal RNA identified elevated expression of transcripts related to angiogenesis (ANGPTL2, HIF-1 alpha, MDK, c-MET, VEGF, TIMP-2), cell proliferation (PRL, IGFBP1, NTSR2, PCSK1), metastasis (ADAM9, ECM1, POSTN) and steroid biosynthesis (CYP17A1 and STS). A number of muscle-restricted transcripts (ITGB1BP3/MIBP, MYF5, MYF6 and TRIM63) were also identified, strengthening the case for a muscle cell progenitor as the origin of disease. Transcript differentials were validated using real-time PCR and subsequent immunohistochemical analysis confirmed protein expression for several of the most interesting changes (MDK, c-MET, VEGF, POSTN, CYP17A1, ITGB1BP3/MIBP and TRIM63).
  
  
  CONCLUSIONS
  Results from this first comprehensive study of ASPS gene expression identifies several targets involved in angiogenesis, metastasis and myogenic differentiation. These efforts represent the first step towards defining the cellular origin, pathogenesis and effective treatment strategies for this atypical malignancy.
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Stockwin@ncifcrf.gov
authors.forename: Luke H
authors.initials: LH
authors.lastname: Stockwin
authors.forename: David T
authors.initials: DT
authors.lastname: Vistica
authors.forename: Susan
authors.initials: S
authors.lastname: Kenney
authors.forename: David S
authors.initials: DS
authors.lastname: Schrump
authors.forename: Donna O
authors.initials: DO
authors.lastname: Butcher
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018234:Sarcoma, Alveolar Soft Part / Q000235:genetics* / Q000556:secondary; D055815:Young Adult