Management of GIST—go beyond imatinib: treat resistant subtypes

Pantaleo, Maria Abbondanza; Biasco, Guido

doi:10.1038/nrclinonc.2015.107

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…In fact, almost all KIT / PDGFRA alterations, but the PDGFRA p.D842V mutation, are activating the tyrosine kinases. KIT / PDGFRA mutations are present in around 85% of GISTs, the other 10-15% cases are usually characterized by mutations in SDH , NF1 or BRAF 92 , 93 . KIT / PDGFRA alterations are usually tested by direct sequencing and NGS technologies.…”

Section: Other Current and Potential Biomarkers With Clinical Impactmentioning

confidence: 99%

Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice

et al. 2020

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Summary The pathologist emerged in the personalized medicine era as a central actor in the definition of the most adequate diagnostic and therapeutic algorithms. In the last decade, gastrointestinal oncology has seen a significantly increased clinical request for the integration of novel prognostic and predictive biomarkers in histopathological reports. This request couples with the significant contraction of invasive sampling of the disease, thus conferring to the pathologist the role of governor for both proper pathologic characterization and customized processing of the biospecimens. This overview will focus on the most commonly adopted immunohistochemical and molecular biomarkers in the routine clinical characterization of gastrointestinal neoplasms referring to the most recent published recommendations, guidelines and expert opinions.

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Section: Other Current and Potential Biomarkers With Clinical Impactmentioning

confidence: 99%

Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice

et al. 2020

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The rs17084733 variant in the KIT 3’ UTR disrupts a miR-221/222 binding site in gastrointestinal stromal tumour: a sponge-like mechanism conferring disease susceptibility

et al. 2019

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Several miRNAs are dysregulated in gastrointestinal stromal tumours (GIST), and miR-221/222 appear to have a prominent role in GIST biology. Therefore, we investigated the role of DNA variants located in miR-221/222 precursor sequences and their target KIT 3'UTR. Ninety-five polymorphisms were analysed in 115 GIST cases and 88 healthy controls. KIT 3'UTR rs17084733 and pri-miR-222 rs75246947 were found significantly associated with GIST susceptibility. Specifically, KIT rs17084733 A allele was more common in GIST, particularly in KIT wild-type (WT) patients (Padj = 0.017). rs17084733 variant is located within one of the three miR-221/222 binding sites in the KIT 3'UTR, resulting in a mismatch in this seed region. Conversely, KIT mRNA levels were lower in patients carrying the variant allele, except for KIT mutant GIST. Luciferase assay data in GIST cells, generated using a construct containing all the three miR-221/222 binding sites, are consistent with KIT mRNA levels in GIST patients. Reporter assay data, generated using a construct containing only the site encompassing rs17084733, confirmed that this is a functional variant disrupting the miR-221/222 binding site. In conclusion, this is the first study investigating the role of SNPs on miR-221/222 precursor sequences and their binding region on KIT 3'UTR in GIST. We identified the KIT variant rs17084733 as a possible novel genetic biomarker for risk of developing KIT -WT GIST. Moreover, our findings suggest the role of one of the three miR-221/222 binding sites on KIT 3'UTR as endogenous sponge, soaking up and subtracting miR-221/222 to the other two sites characterized by a higher affinity.

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Integrating miRNA and Gene Expression Profiling Analysis Revealed Regulatory Networks in Gastrointestinal Stromal Tumors

et al. 2016

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Management of GIST—go beyond imatinib: treat resistant subtypes

Abstract: Refers toBlay, J.-Y. et al. Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial. Lancet Oncol. 16, 550-560 (2015)

Cited by 3 publications

References 10 publications

Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice

Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice

The rs17084733 variant in the KIT 3’ UTR disrupts a miR-221/222 binding site in gastrointestinal stromal tumour: a sponge-like mechanism conferring disease susceptibility

Integrating miRNA and Gene Expression Profiling Analysis Revealed Regulatory Networks in Gastrointestinal Stromal Tumors

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