title: Differential expression of neural markers in KIT and PDGFRA wild-type gastrointestinal stromal tumours.
abstract: OBJECTIVE
  To compare the genomic signatures of wild-type (WT) and mutated GISTs and the murine interstitial cells of Cajal (ICCs) to find markers of cell differentiation and other functions that may identify cells that give rise to WT tumours.
  
  
  RESULTS
  We analysed the gene expression profiles of a total of 30 tumour samples (four WT GISTs and 26 mutated GISTs), selected the genes most differentially expressed (P < 0.001:448 probe sets) and validated these results by quantitative polymerase chain reaction (PCR) and immunohistochemistry. In addition, we conducted a meta-analysis merging data from human GISTs with a genomic data set from murine ICCs. The gene expression profiles of WT and mutated GISTs differed profoundly, especially in the expression of those genes restricted primarily to neural tissues. We found that mature ICCs are more similar to mutated GISTs than WT GISTs.
  
  
  CONCLUSIONS
  WT GISTs have different genomic profiles from both mutated GISTs and murine mature ICCs. Considering that IGF1R expression is common to both WT GISTs and putative precursor ICCs, this study suggests that WT GISTs may derive either from ICCs at a different step of differentiation or from a different cell of origin.
authors.affiliation: Department of Hematology and Oncology Sciences, L A Seragnoli, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. maria.pantaleo@unibo.it
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pantaleo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.forename: Margherita
authors.initials: M
authors.lastname: Nannini
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Serena
authors.initials: S
authors.lastname: Formica
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Christopher
authors.initials: C
authors.lastname: Corless
authors.forename: Angelo Paolo
authors.initials: AP
authors.lastname: Dei Tos
authors.forename: Paola
authors.initials: P
authors.lastname: Paterini
authors.forename: Fausto
authors.initials: F
authors.lastname: Catena
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maleddu
authors.forename: Maristella
authors.initials: M
authors.lastname: Saponara
authors.forename: Monica
authors.initials: M
authors.lastname: Di Battista
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D004252:DNA Mutational Analysis; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D019089:Stem Cell Factor / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D019089:Stem Cell Factor; D020797:Receptor, Platelet-Derived Growth Factor beta