Gene expression patterns of hemizygous and heterozygous KIT mutations suggest distinct oncogenic pathways: a study in NIH3T3 cell lines and GIST samples.

摘要: Objective Most gain of function mutations tyrosine kinase receptors in human tumours are hemizygous. Gastrointestinal stromal (GIST) with homozygous have a worse prognosis. We aimed to identify genes differentially regulated by hemizygous and heterozygous KIT mutations. Materials Methods Expression 94 384 miRNA was analysed low density arrays five NIH3T3 cell lines expressing the full-length cDNA wild-type (WT), mutation del557-558 (D6) or del564-581 (D54) WT/D6 WT/D54. Expression 5 these then GISTs samples. Results Unsupervised supervised hierarchical clustering mRNA profiles showed that mutants clustered WT cells while were distinct. Among cells, D6 D54 separately. Most deregulated been reported as potentially implicated cancer severals, ANXA8 FBN1, highlighted both, analyses. MiRNA analyses samples confirmed their expressions varied according alleles. Interestingly, RGS16, membrane protein regulator G family, correlate subcellular localization might be responsible for regulation PI3K/AKT signalling pathway. Conclusion Patterns expression depend on heterozygous/hemizygous status mutations, deletion/presence TYR568 & TYR570 residues. Thus each may drive specific oncogenic pathways.