Differential expression of neural markers in KIT and PDGFRA wild-type gastrointestinal stromal tumours

Maria A. Pantaleo, Annalisa Astolfi, Margherita Nannini, Claudio Ceccarelli, Serena Formica, Donatella Santini, Michael C. Heinrich, Christopher Corless, Angelo Paolo Dei Tos, Paola Paterini, Fausto Catena, Alessandra Maleddu, Maristella Saponara, Monica di Battista, Guido Biasco

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Aims: 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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)1071-1080
Number of pages10
JournalHistopathology
Volume59
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • GIST
  • Gene expression profiling
  • ICC
  • ICC mature
  • ICC precursor
  • IGF1R
  • KIT
  • PDGFRA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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