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Sergei Boichuk, Aigul Galembikova, Pavel Dunaev, Ekaterina Micheeva, Elena Valeeva, Maria Novikova, Natalya Khromova, Pavel Kopnin
Dysregulation of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling pathway is frequently observed in multiple human malignancies, and thus, therapeutic strategies targeting FGFs and FGFRs in human cancer are being extensively explored. We observed the activation of the FGF/FGFR-signaling pathway in imatinib (IM)-resistant gastrointestinal stromal tumor (GIST) cells. Furthermore, we found that the activation of FGFR signaling has a significant impact on IM resistance in GISTs in vitro...
October 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kaitlin Stanley, Erika Friehling, Amy Davis, Sarangarajan Ranganathan
Gastrointestinal stromal tumors (GISTs) are rare in children. Succinate dehydrogenase (SDH)-deficient GISTs are wild type and lack KIT proto-oncogene receptor tyrosine kinase and platelet-derived growth factor receptor A ( KIT or PDGFRA) mutations. These tumors result from germline SDH mutations, somatic SDH mutations, or SDH epimutants. Germline mutations in SDH genes ( SDHA, SDHB, SDHC, or SDHD) suggest Carney-Stratakis syndrome, a paraganglioma syndrome with predisposition for GIST. Negative immunohistochemistry for SDHB indicates dysfunction of the mitochondrial complex regardless of the subunit affected...
October 9, 2018: Pediatric and Developmental Pathology
Fei Xu, Xiaohong Ma, Yichen Wang, Yuan Tian, Wei Tang, Meng Wang, Ren Wei, Xinming Zhao
OBJECTIVE: To evaluate CT texture analysis as a tool to differentiate gastrointestinal stromal tumors (GISTs) without KIT exon 11 mutation. MATERIALS AND METHODS: This study consisted of a study group of 69 GISTs and a validation group of 17 GISTs. Clinical information of the patients were collected and analyzed. Two-dimensional and three-dimensional texture analysis was performed. The textural parameters were evaluated in the study group and were validated in the validation group...
October 2018: European Journal of Radiology
I Bure, F Haller, D V Zaletaev
Gastrointestinal stromal tumours are the most common mesenchymal tumours of the gastrointestinal tract. Despite similar mutation pattern of activating mutations in KIT or PDGFRA receptors in 85% of cases, they demonstrate significantly heterogeneous clinical behaviour and pathological characteristics. This heterogeneity opens the question of the role of other factors and mechanisms of regulation in the development of GIST. Additional mutations in downstream effectors of GIST related signalling pathways or aberrant expression of non-coding RNAs may be additional contributing factors, the latter being increasingly recognized in carcinogenesis in general...
October 4, 2018: Current Molecular Medicine
G N Wali, D Halliday, J Dua, E Ieremia, T McPherson, R N Matin
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours arising in the gastrointestinal tract. Early detection, before metastasis occurs, is important as complete surgical excision achieves cure. Approximately 85% of GISTs are associated with mutations in the KIT gene, and although the majority of GISTs are sporadic, familial GISTs have been identified. Several families with multiple GIST tumours have also been described with various cutaneous findings including hyperpigmentation, multiple lentigines, vitiligo and urticaria pigmentosa...
October 2, 2018: Clinical and Experimental Dermatology
Yemarshet K Gebreyohannes, Agnieszka Wozniak, Madalina-Elena Zhai, Jasmien Wellens, Jasmien Cornillie, Ulla Vanleeuw, Erica K Evans, Alexandra K Gardino, Christoph Lengauer, Maria Debiec-Rychter, Raf Sciot, Patrick Schöffski
PURPOSE: Gastrointestinal stromal tumors (GIST) are commonly treated with tyrosine kinase inhibitors (TKI). The majority of patients with advanced GIST ultimately become resistant to TKI due to acquisition of secondary KIT mutations, while primary resistance is mainly caused by PDGFR A p.D842V mutation. We tested the activity of avapritinib, potent and highly selective inhibitor of mutated KIT and PDGFRA, in three patient-derived xenograft (PDX) GIST models carrying different KIT mutations, with differential sensitivity to standard TKI...
October 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Samuel J Klempner, Kyle Gowen, Thomas K Lee, Viola W Zhu, Alexa B Schrock, Vincent A Miller, Siraj M Ali, Sai-Hong Ignatius Ou
Non-small cell lung cancer (NSCLC) has emerged as a paradigm for clinical application of precision medicine as optimal therapy is commonly chosen based on genomic biomarkers identified in a patient's tumor sample. Recurrent driver alterations are well described, however, a need to continually identify rare variants remains clinically relevant. We identified an incident case of advanced NSCLC with a PDGFR-α N848 K activation loop mutation with no other concurrent oncogenic drivers. Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST...
October 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Charlotte Cohen, Daniel Pop, Philippe Icard, Jean-Philippe Berthet, Nicolas Venissac, Jérome Mouroux
BACKGROUND:  Esophageal gastrointestinal stromal tumors (E-GISTs) represent less than 1% of all GISTs. The rarity of this lesion precludes the realization of randomized studies, and its treatment remains a matter of debate. We aimed to evaluate the feasibility of enucleation by video-assisted thoracic surgery (VATS) for low- to intermediate-risk E-GIST. METHODS:  We performed a retrospective review of patients treated by enucleation through VATS between January 2004 and January 2014 and reviewed the literature...
September 28, 2018: Thoracic and Cardiovascular Surgeon
Christian Pesenti, Erwan Bories, Fabrice Caillol, Jean Philippe Ratone, Sebastien Godat, Genevieve Monges, Flora Poizat, Jean Luc Raoul, Pauline Ries, Marc Giovannini
Background and Objectives: Subepithelial lesions (SELs) of the upper part of the digestive tract are rare, and it can be difficult to characterize them. Recently, contrast-enhanced endosonography (EUS) and elastometry have been reported as useful adjuncts to EUS and EUS-guided fine needle aspiration (EUS-FNA) in cases of pancreatic mass and lymph node involvement. The aim of this retrospective analysis was to evaluate whether contrast-enhanced EUS can discriminate benign submucosal lesions from malignant ones...
September 26, 2018: Endoscopic Ultrasound
Chairat Supsamutchai, Chumpon Wilasrusmee, Pitichote Hiranyatheb, Jakrapan Jirasiritham, Teerawut Rakchob, Pattawia Choikrua
Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The major risk factors of recurrence and metastasis are mitotic index and tumor size. This study investigates the risk of recurrence and metastasis in solely gastric GIST. The primary outcome is to evaluate risk of recurrence and metastasis. The secondary outcome is to analyse survival rates of patients who have recurrence and metastasis after curative resection. Method: A cohort of patients who underwent curative resection of gastric GIST between January 2006 to December 2016 was reviewed...
November 2018: Annals of Medicine and Surgery
Xuquan Jing, Xue Meng, Yongsheng Gao, Jinming Yu, Bo Liu
Gastrointestinal stromal tumors (GISTs) are very uncommon in pediatric patients, and they are distinct clinical-pathological and molecular deviations from their adult counterparts. Most pediatric GISTs lack the c-kit or platelet-derived growth factor receptor alpha (PDGFRA) genes mutations. To date, there is no published standard guidelines available for the best treatment of pediatric GISTs, especially for infant GIST. Therefore, we report a case of 4-month-old infant with GIST of mesocolon without KIT/PDGFRA mutation...
September 25, 2018: Cancer Biology & Therapy
Lillian R Klug, Amber E Bannon, Nathalie Javidi-Sharifi, Ajia Town, William H Fleming, Judy K VanSlyke, Linda S Musil, Jonathan A Fletcher, Jeffrey W Tyner, Michael C Heinrich
Certain cancers, including gastrointestinal stromal tumor (GIST) and subsets of melanoma, are caused by somatic KIT mutations that result in KIT receptor tyrosine kinase constitutive activity, which drives proliferation. The treatment of KIT-mutant GIST has been revolutionized with the advent of KIT-directed cancer therapies. KIT tyrosine kinase inhibitors (TKI) are superior to conventional chemotherapy in their ability to control advanced KIT-mutant disease. However, these therapies have a limited duration of activity due to drug-resistant secondary KIT mutations that arise (or that are selected for) during KIT TKI treatment...
September 21, 2018: Oncogene
Gloria Ravegnini, Milena Urbini, Vittorio Simeon, Chiara Genovese, Annalisa Astolfi, Margherita Nannini, Lidia Gatto, Maristella Saponara, Manuela Ianni, Valentina Indio, Giovanni Brandi, Stefania Trino, Patrizia Hrelia, Guido Biasco, Sabrina Angelini, Maria A Pantaleo
Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite  the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process...
September 20, 2018: Pharmacogenomics Journal
Olivier Bouché, Axel Le Cesne, Maria Rios, Loic Chaigneau, Antoine Italiano, Florence Duffaud, Thierry Lecomte, Dominique Arsène, Sylvain Manfredi, Thomas Aparicio, Stéphane Remy, Nicolas Isambert, Olivier Collard, Frank Priou, François Bertucci, Roland Sambuc, Ségolene Bisot-Locard, Olivier Bourges, Sylvie Chabaud, Jean-Yves Blay
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. EPIdemiology GIST, is an observational multicenter longitudinal follow-up cohort study reporting the prescribing patterns of imatinib in patients with GIST and the impact of the treatment in a real-world (standard clinical) setting. METHODS: Eligible patients had a confirmed diagnosis of unresectable or metastatic KIT-positive GIST and started treatment with imatinib for the first time between May 24, 2002, and June 30, 2010...
2018: PloS One
Siyuan Tan, Ping Chen, Jiafu Ji, Shanshan Guo, Dapeng Yu, Tetsuya Asakawa, Yu Zhou, Masanobu Abe, Liang Zong
Objectives: Sunitinib (a second-line chemotherapeutic agent that inhibits multiple kinases, including KIT and PDGFR) is widely used in imatinib-resistant patients with gastrointestinal stromal tumors (GISTs). However, diverse responses to sunitinib have been observed in the clinic. We aimed to evaluate whether the different GIST genotypes could be used to stratify patient response to sunitinib. Methods: We searched the PubMed, Embase, and Cochrane databases and included English-language literature published up to August 31, 2017...
2018: Disease Markers
Wen-Jie Wang, Hong-Tao Li, Jian-Ping Yu, Yu-Min Li, Xiao-Peng Han, Peng Chen, Wen-Wen Yu, Wei-Kai Chen, Zuo-Yi Jiao, Hong-Bin Liu
Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet‑derived growth factor receptor α (PDGFRA) wild‑type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild‑type GIST samples compared with KIT/PDGFRA mutant GIST samples...
September 5, 2018: Molecular Medicine Reports
César Vivian Lopes, Péttala Rigon, Cláudio Galleano Zettler, Antônio Atalíbio Hartmann
OBJECTIVES: To evaluate the diagnostic yield of the cell block (CB) technique with immunohistochemistry in patients with mesenchymal neoplasms of the gastrointestinal tract collected by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). METHODS: Tissue samples from consecutive patients with subepithelial lesions collected by EUS-FNA, without analysis by on-site cytopathology, were evaluated by the same pathologist only using CBs in AAF fixative. Sections were stained with haematoxylin-eosin and underwent complementary immunohistochemical staining for SMA, CD117, DOG-1 and S100 in the presence of mesenchymal neoplasms...
September 15, 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
C Yamashita, A Otsuka, M Nomura, T Honda, K Kabashima
No abstract text is available yet for this article.
September 10, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Bruno Vincenzi, Margherita Nannini, Giuseppe Badalamenti, Giovanni Grignani, Elena Fumagalli, Silvia Gasperoni, Lorenzo D'Ambrosio, Lorena Incorvaia, Marco Stellato, Mariella Spalato Ceruso, Andrea Napolitano, Sergio Valeri, Daniele Santini, Giuseppe Tonini, Paolo Giovanni Casali, Angelo Paolo Dei Tos, Maria Abbondanza Pantaleo
Background: Rechallenge with imatinib is an option in advanced gastrointestinal stromal tumor (GIST) patients following progression with standard tyrosine-kinase inhibitors (TKIs), imatinib, sunitinib and regorafenib. We retrospectively collected data from metastatic Italian GIST patients treated with imatinib resumption after progression to conventional TKIs. Methods: A total of 104 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected from six referral Italian institutions...
2018: Therapeutic Advances in Medical Oncology
Caspar Franck, Rosa Rosania, Sabine Franke, Johannes Haybaeck, Ali Canbay, Marino Venerito
BACKGROUND: Sorafenib has shown efficacy in patients with imatinib-, sunitinib-, and regorafenib-resistant gastrointestinal stromal tumors (GISTs). No biomarker is currently available for predicting response to sorafenib in patients with GIST. METHODS: We herein report 3 patients with imatinib-, sunitinib-, and regorafenib-resistant metastasized GISTs, who were treated with sorafenib. Besides receptor tyrosine kinase KIT and platelet-derived growth factor receptor α, also BRAF was tested for mutations...
September 4, 2018: Digestion
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