Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients – A GIRCG study

Capelli, Laura; Petracci, Elisabetta; Quagliuolo, Vittorio; Saragoni, Luca; Colombo, Piergiuseppe; Morgagni, Paolo; Calistri, Daniele; Tomezzoli, Anna; Cosmo, M. Di; Roviello, Franco; Vindigni, Carla; Coniglio, Arianna; Villanacci, Vincenzo; Catarci, Marco; Coppola, Luigi; Alfieri, Sergio; Ricci, Riccardo; Capella, Carlo; Rausei, Stefano; Gulino, D.; Amadori, Dino; Ulivi, Paola

doi:10.1016/j.ejso.2016.05.022

Cited by 20 publications

(12 citation statements)

References 34 publications

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“…The major driving elements in GIST pathogenesis are linked with mutations in tyrosine kinase family (KIT) or platelet-derived growth factor (PDGFRA) gene [ 1 , 2 ]. Only a small proportion of GISTs appear to be associated with neither KIT or PDGFR sporadic mutations and are referred to as wild-type (WT) tumors [ 3 ]. GISTs most commonly arise from the fourth layer of the gastrointestinaltract wall (muscularis propria), and less often from the more superficial muscularis mucosa layer [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

Kupčinskas

2018

IJMS

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of gastrointestinal tract. GISTs have very different clinical phenotypes and underlying molecular characteristics that are not yet completely understood. microRNAs (miRNAs) have been shown to participate in carcinogenesis pathways through post-transcriptional regulation of gene expression in different tumors. Over the last years emerging evidence has highlighted the role of miRNAs in GISTs. This review provides an overview of original research papers that analyze miRNA deregulation patterns, functional role, diagnostic, therapeutic and prognostic implications in GIST as well as provides directions for further research in the field.

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Section: Introductionmentioning

confidence: 99%

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

Kupčinskas

2018

IJMS

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“…In a previous study, the clinical model was used to predict the biological behaviors of GISTs (25), and genotypes have been shown to be closely related to certain clinical characteristics (26)(27)(28). However, the relationship between some clinical characteristics and the KIT 11 mutation remains controversial (26,27,29,30). Most of the previous studies showed that GISTs with the KIT exon 11 mutation usually had high percentages of mitotic count and/or poor prognosis (26,27,30).…”

Section: Discussionmentioning

confidence: 99%

“…However, the relationship between some clinical characteristics and the KIT 11 mutation remains controversial (26,27,29,30). Most of the previous studies showed that GISTs with the KIT exon 11 mutation usually had high percentages of mitotic count and/or poor prognosis (26,27,30). The relationship between CA724 and GIST genotypes has not been reported until now.…”

Section: Discussionmentioning

confidence: 99%

Value of contrast-enhanced CT based radiomic machine learning algorithm in differentiating gastrointestinal stromal tumors with KIT exon 11 mutation: a two-center study

Liu¹,

Wang²,

Liu³

et al. 2020

Preprint

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Background Knowing the genetic phenotype of gastrointestinal stromal tumors (GISTs) is essential for patients who receive therapy with tyrosine kinase inhibitors.Methods We enrolled 106 patients (80 in the training set, 26 in the validation set) with clinicopathologically confirmed GISTs from two centers. Preoperative and postoperative clinical characteristics were selected and analyzed to construct the clinical model. Arterial phase (A-phase), venous phase (V-phase), delayed phase (D-phase), and combined radiomics algorithms were generated from the training set based on contrast-enhanced computed tomography (CE-CT) images. Various radiomics feature selection methods were used, namely least absolute shrinkage and selection operator (LASSO); minimum redundancy maximum relevance (mRMR); and generalized linear model (GLM) as a machine-learning classifier. Independent predictive factors were determined to construct preoperative and postoperative radiomics nomograms by multivariate logistic regression analysis. The performances of the clinical model, radiomics algorithm, and radiomics nomogram in distinguishing GISTs with the KIT exon 11 mutation were evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC).Results The combined radiomics algorithm was found to be the best prediction model for differentiating the expression status of the KIT exon 11 mutation (AUC = 0.836; 95% confidence interval (CI), 0.640–0.951) in the validation set. The clinical model, and preoperative and postoperative radiomics nomograms had AUCs of 0.606 (95% CI, 0.397–0.790), 0.715 (95% CI, 0.506–0.873), and 0.679 (95% CI, 0.468–0.847), respectively, with the validation set.Conclusion The radiomics algorithm could distinguish GISTs with the KIT exon 11 mutation based on CE-CT images and could potentially be used for selective genetic analysis to support the precision medicine of GISTs.

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“…The re-sults of published studies shows that KIT mutations in exon 11 can be linked with more aggressive tumor behavior 17,18 . Capelli et al 19 showed that the patients with gastric GIST who had the KIT mutations, were presented with worse pathological parameters, such as tumor necrosis, spindle cellularity, tumor size and mitotic index. Similar results were noted by Schaefer et al 20 .…”

Section: Discussionmentioning

confidence: 99%

Significance of KIT and PDGFRA mutations in gastric gist imatinib - naive surgically treated patients

et al. 2019

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Background/Aim. KIT (KIT proto-oncogene receptor tyrosine kinase) and PDGFRA (platelet-derived growth factor receptor alpha) gene mutations represent major molecular forces inside the gastrointestinal stromal tumors (GIST). Aim of this study was to evaluate these mutations in the patients who underwent surgical resection of gastric GIST, but without imatinib mesylate treatment. Methods. Retrospective clinical study included patients who were operated on due to gastric GIST from November 2000 till November 2016. A molecular analysis of paraffin embedded tumor tissue was performed, and the patients with the presence of KIT and PDGFRA mutations were further evaluated, with regard to the pathological tumor stage, disease recurrence and overall survival. Results. Out of 45 patients in total, 43 patients had KIT and PDGFRA mutations, and 2 patients were classified as the wild type GIST. After curative resection, 11 patients were classified as a low risk GIST, 8 as an intermediate risk and 26 as a high risk GIST. The KIT mutations were present in 37 patients, most commonly as deletion in exon 11. The PDGFRA mutations were present in 6 patients. The presence of KIT mutation had a strong statistical correlation with the mitotic index (p = 0.021). After the ten-year follow-up, all patients with the PDGFRA mutations were alive, while those with the KIT mutations had a survival rate of 71% (p = 0.31). Conclusion. The presence of KIT exon 11 deletion in the patients with primarily resected gastric GIST is associated with the higher mitotic index and worse overall survival than those present with the PDGFRA mutations. This results suggest prognostic significance towards more aggressive behaviors. ApstraktUvod/Cilj. KIT (KIT proto-oncogene receptor tyrosine kinase) i PDGFRA (Platelet-derived growth factor receptor alpha) genske mutacije predstavljaju osnovne molekularne promene u grupi gastrointestinalnih stromalnih tumora (GIST). Cilj ove studije bio je da se analiziraju KIT i PDGFRA mutacije u grupi bolesnika koji su operisani zbog primarnog GIST-a želuca, ali bez terapije imatinib mesilatom. Metode. Načinjena je retrospektivna klinička studija koja je uključila bolesnike operisane zbog GIST-a želuca u periodu od novembra 2000. do novembra 2016. godine. Načinjena je molekularna analiza na parafinskim kalupima tumorskog tkiva, a kod bolesnika kod kojih su identifikovane KIT i PDGFRA mutacije sprovedena je dalja analiza, sa posebnim osvrtom na patološke karakteristike tumora, recidiv oboljenja i ukupno preživljavanje, te procena uticaja analiziranih genskih mutacija na navedene promene. Rezultati. Od ukupno 45 bolesnika, 43 bolesnika imala su prisutne mutacije na KIT i PDGFRA genima, dok su dva bolesnika klasifikovani kao "wild type" GIST. Po učinjenoj kurativnoj resekciji, 11 bolesnika je klasifikovano u grupu GIST-a niskog stepena, 8 u grupu srednjeg, a 26 bolesnika u grupu visokog rizika od metastaziranja. KIT mutacije su bile prisutne kod 37 bolesnika, najčešće u formi deleciji na egzonu 11. PDGFRA mutacije bile su prisutne...

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Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients – A GIRCG study

Cited by 20 publications

References 34 publications

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

Small Molecules in Rare Tumors: Emerging Role of MicroRNAs in GIST

Value of contrast-enhanced CT based radiomic machine learning algorithm in differentiating gastrointestinal stromal tumors with KIT exon 11 mutation: a two-center study

Significance of KIT and PDGFRA mutations in gastric gist imatinib - naive surgically treated patients

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