<i>KIT, DOG1, PDGFR</i>, and <i>IGFR1</i> gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients.

Broto, Javier Martín; Muro, Xavier García del; Gutiérrez, Alberto; Martínez‐Trufero, Javier; Serrano, Teresa; Rubio, Joaquín Casal; Laínez, Núria; Sevilla, Isabel; Cruz, Jose Vinicius; Ramos, Rafael; Ortega, Luís; Poveda, Andrés; Ramírez, Marcos; Cubedo, Ricardo; Löpez‐Guerrero, José Antonio

doi:10.1200/jco.2011.29.15_suppl.10047

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“…Bioinformatic analysis suggested that miRNA221 and miRNA222 targeted the 3′ UTR of KIT mRNA, downregulating KIT protein expression, which inhibited normal erythropoiesis and erythroleukemic cell growth [ 19 ]. Based on these observations our group had shown the prognostic relevance of these miRNAs, in a KNGL series, as well as, its correlation with KIT expression [ 20 ]. At the same time, Koelz and colleagues published in 2011, that miRNA221/222 expression levels were significantly overexpressed in KNGL, indicating both publications that this miRNA cluster acts as a regulator of KIT expression.…”

Section: Introductionmentioning

confidence: 99%

Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients

et al. 2018

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IntroductionThere are limited findings available on KIT-negative GIST-like (KNGL) population. Also, KIT expression may be post-transcriptionally regulated by miRNA221 and miRNA222. Hence, the aim of this study is to characterize KNGL population, by differential gene expression, and to analyze miRNA221/222 expression and their prognostic value in KNGL patients.MethodsKIT, PDGFRA, DOG1, IGF1R, MIR221 and MIR222 expression levels were determined by qRT-PCR. We also analyzed KIT and PDGFRA mutations, DOG1 expression, by immunohistochemistry, along with clinical and pathological data. Disease-free survival (DFS) and overall survival (OS) differences were calculated using Log-rank test.ResultsHierarchical cluster analyses from gene expression data identified two groups: group I had KIT, DOG1 and PDGFRA overexpression and IGF1R underexpression and group II had overexpression of IGF1R and low expression of KIT, DOG1 and PDGFRA. Group II had a significant worse OS (p = 0.013) in all the series, and showed a tendency for worse OS (p = 0.11), when analyzed only the localized cases. MiRNA222 expression was significantly lower in a control subset of KIT-positive GIST (p < 0.001). OS was significantly worse in KNGL cases with higher expression of MIR221 (p = 0.028) or MIR222 (p = 0.014).ConclusionsWe identified two distinct KNGL subsets, with a different prognostic value. Increased levels of miRNA221/222, which are associated with worse OS, could explain the absence of KIT protein expression of most KNGL tumors.

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Section: Introductionmentioning

confidence: 99%