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met exon 14

Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
Karin Jasek, Veronika Buzalkova, Gabriel Minarik, Andrea Stanclova, Peter Szepe, Lukas Plank, Zora Lasabova
Gastrointestinal stromal tumors (GISTs) are characterized by mutations in exons 9, 11, 13, and 17 of KIT or exons 12, 14, and 18 of PDGFRA gene. However, approximately 10 to 15 % of GISTs lack the mutations in KIT and PDGFRA, and these are referred to as wild-type GISTs which are less sensitive to tyrosine-kinase inhibitors. The aim of this study was to detect BRAF mutations in patients with wild-type GISTs. We applied a sensitive allele-specific PCR, which was optimized using the V600E mutation-harboring cell line RKO, followed by verification of the results by dideoxy sequencing...
November 18, 2016: Virchows Archiv: An International Journal of Pathology
Cristina Aguado, Ana Giménez-Capitán, Niki Karachaliou, Ana Pérez-Rosado, Santiago Viteri, Daniela Morales-Espinosa, Rafael Rosell
Obtaining a biopsy of solid tumors requires invasive procedures that strongly limit patient compliance. In contrast, a blood extraction is safe, can be performed at many time points during the course disease and encourages appropriate therapy modifications, potentially improving the patient's clinical outcome and quality of life. Fusion of the tyrosine kinase genes anaplastic lymphoma kinase (ALK), C-ROS oncogen 1 (ROS 1), rearranged during transfection (RET) and neurotrophic tyrosine kinase 1 (NTRK1) occur in 1-5% of lung adenocarcinomas and constitute therapeutic targets for tyrosine kinase inhibitors...
October 2016: Translational Lung Cancer Research
Alexander Drilon, Federico Cappuzzo, Sai-Hong Ignatius Ou, D Ross Camidge
The mesenchymal epithelial transition factor receptor (MET) is a potential therapeutic target in a number of cancers, including non-small cell lung cancer (NSCLC). In NSCLC, MET pathway activation is thought to occur via a diverse set of mechanisms that influence properties affecting cancer cell survival, growth, and invasiveness. Preclinical and clinical evidence suggest a role for MET activation as both a primary oncogenic driver in subsets of lung cancer, and as a secondary driver of acquired resistance to targeted therapy in other genomic subsets...
October 26, 2016: Journal of Thoracic Oncology
A Rabeau, I Rouquette, J-M Vantelon, E Taranchon-Clermont, J Mazières
Targeted therapy in lung cancer changes the prognostic and treatment of patients. MET is an oncogene including exon 14 mutations and gene amplification associated with worse prognosis. We here report the case of a 47-year-old former smoker, woman, with a stage IV lung adenocarcinoma with multiple chemotherapy failure. A MET amplification was identified and the patient consequently received crizotinib. A major response was observed after eight weeks of treatment. MET amplification screening appears to be interesting with some oncogenic-addicted tumor response rate...
October 13, 2016: Revue des Maladies Respiratoires
Sana Saif Ur Rehman, Suresh S Ramalingam
Advanced stage nonsmall cell lung cancer had been treated mainly with platinum-based doublet chemotherapy, and other cytotoxic agents that offered significant survival advantage over best supportive care, until recently. Modest improvements were achieved with the addition of antibodies targeting the vascular endothelial growth factor, and the introduction of maintenance chemotherapy. Improvements in our knowledge of lung cancer biology have shifted the current treatment paradigm from being based on histology to one based on molecular biomarkers...
October 2016: Seminars in Respiratory and Critical Care Medicine
Samuel J Klempner, Ali Borghei, Behrooz Hakimian, Siraj M Ali, Sai-Hong Ignatius Ou
INTRODUCTION: A significant portion of NSCLCs with MET Proto-Oncogene, Receptor Tyrosine Kinase gene (MET) exon 14 skipping alterations are sensitive to small-molecule mesenchymal-epithelial transition tyrosine kinase inhibitors. However, the incidence and management of brain metastases in this molecular subset is unknown and represents an unmet clinical need. METHODS: Hybrid capture-based comprehensive genomic profiling identified a patient with a MET exon 14 skipping alteration, and serial magnetic resonance imaging was utilized to follow intracranial disease during crizotinib and subsequent cabozantinib therapy...
September 28, 2016: Journal of Thoracic Oncology
David Arguello, Andreas Voss, Zoran Gatalica, Ryan Bender
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Sai-Hong Ignatius Ou, Lauren Young, Alexa B Schrock, Adrienne Johnson, Samuel J Klempner, Viola W Zhu, Vincent A Miller, Siraj M Ali
INTRODUCTION: MET exon14 skipping (METex14) alterations represent a unique subset of oncogenic drivers in non-small cell lung cancer (NSCLC). Preliminary clinical activity of crizotinib against METex14+ NSCLC has been reported. The full spectrum of resistance mechanisms to crizotinib in METex14+ NSCLC remains to be identified. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) performed on a tumor specimen obtained at diagnosis and a hybrid capture-based assay of circulating tumor DNA (ctDNA) at the time of progression on crizotinib was assessed in a pairwise fashion...
September 22, 2016: Journal of Thoracic Oncology
Rafael Caparica, Cheng Tzu Yen, Renata Coudry, Sai-Hong Ignatius Ou, Marileila Varella-Garcia, D Ross Camidge, Gilberto de Castro
MET activation highly sensitive to MET inhibition has recently been described in non-small cell lung cancer (NSCLC) through two mechanisms: high-level amplification of the MET gene (usually expressed relative to the centromere on chromosome 7 when using fluorescence in-situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other, or if both can represent true oncogenic driver states continues to be explored. Cases of MET inhibitor sensitive NSCLC harboring exon 14 alterations without co-incident amplification have already been described...
September 21, 2016: Journal of Thoracic Oncology
Shiyong Li, Yoon-La Choi, Zhuolin Gong, Xiao Liu, Maruja Lira, Zhengyan Kan, Ensel Oh, Jian Wang, Jason C Ting, Xiangsheng Ye, Christoph Reinhart, Xiaoqiao Liu, Yunfei Pei, Wei Zhou, Ronghua Chen, Shijun Fu, Gang Jin, Awei Jiang, Julio Fernandez, James Hardwick, Min Woong Kang, Hoseok I, Hancheng Zheng, Jhingook Kim, Mao Mao
INTRODUCTION: The incidence rate of lung adenocarcinoma (LUAD), the predominant histological subtype of lung cancer, is elevated in Asians, particularly in female nonsmokers. The mutation patterns in LUAD in Asians might be distinct from those in LUAD in whites. METHODS: We profiled 271 resected LUAD tumors (mainly stage I) to characterize the genomic landscape of LUAD in Asians with a focus on female nonsmokers. RESULTS: Mutations in EGFR, KRAS, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those reported in studies of LUAD in non-Asians...
December 2016: Journal of Thoracic Oncology
Martin Sattler, Ravi Salgia
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Oncology
Yan Yang, Sreekala Mandiyan, Brett S Robinson, Gerald McMahon
A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14-mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb) that block MET-dependent signaling and tumor growth. In particular, the MET mAb KTN0073 and KTN0074 bind the Sema/PSI domain, at overlapping but distinct epitopes, preventing HGF interaction with MET and triggering receptor ubiquitination and degradation...
October 1, 2016: Cancer Research
Kazuya Inoki, Takeshi Nakajima, Shigeki Sekine, Kokichi Sugano, Shunsuke Tsukamoto, Masayoshi Yamada, Michihiro Mutoh, Taku Sakamoto, Takahisa Matsuda, Masau Sekiguchi, Mineko Ushiama, Teruhiko Yoshida, Hiromi Sakamoto, Yukihide Kanemitsu, Yutaka Saito
Although regular colonoscopy surveillance is recommended for patients with Lynch syndrome (LS) who underwent partial colectomy, the appropriate interval has not been determined. We report a case of colorectal cancer (CRC) detected by short-interval surveillance colonoscopy (SC) in a patient with LS having a past history of partial colectomy. A 65-year-old man underwent sigmoidectomy for advanced CRC. His family history revealed that his two younger brothers had CRC in their twenties and thirties, respectively, and the patient met with the criteria in the Revised Bethesda Guidelines...
November 2016: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
Karen L Reckamp, Vladislava O Melnikova, Chris Karlovich, Lecia V Sequist, D Ross Camidge, Heather Wakelee, Maurice Perol, Geoffrey R Oxnard, Karena Kosco, Peter Croucher, Errin Samuelsz, Cecile Rose Vibat, Shiloh Guerrero, Jennifer Geis, David Berz, Elaina Mann, Shannon Matheny, Lindsey Rolfe, Mitch Raponi, Mark G Erlander, Shirish Gadgeel
INTRODUCTION: In approximately 60% of patients with NSCLC who are receiving EGFR tyrosine kinase inhibitors, resistance develops through the acquisition of EGFR T790M mutation. We aimed to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations from urine and plasma specimens is feasible. METHODS: Short footprint mutation enrichment next-generation sequencing assays were used to interrogate EGFR activating mutations and the T790M resistance mutation in urine or plasma specimens from patients enrolled in TIGER-X (NCT01526928), a phase 1/2 clinical study of rociletinib in previously treated patients with EGFR mutant-positive advanced NSCLC...
October 2016: Journal of Thoracic Oncology
Natheir Obeidat, Abdalla Awidi, Nidaa Ababneh, Maha Shomaf, Tariq Al-Adaily, Mohammad Jaber, Mohammad Al-Khateeb, Salah Abbasi
BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) gene have been associated with tumor response to tyrosine kinase inhibitors (TKIs) and favorable outcome in patients with non-small-cell lung cancer (NSCLC). The activating mutations that confer sensitivity to EGFR TKIs are present in the TK domain of the EGFR gene. This study aims to report on the prevalence of EGFR mutations in NSCLC and non-squamous lung cancer patients at diagnosis, using genomic deoxyribonucleic acid (DNA) obtained from paraffin-embedded tissue samples...
April 2016: Journal of Cancer Research and Therapeutics
Caroline E McCoach, Trever G Bivona, Collin M Blakely, Robert C Doebele
Evaluations of resistance mechanisms to targeted treatments in non-small-cell lung cancer (NSCLC) are necessary for development of improved treatment after disease progression and to help delay progression of disease. Populations of cells that survive after initial treatment form the basis of resistance via outgrowth of resistant clones or activation of alternative signaling pathways. In this report we describe a clinical trial approach in which patients with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), C-ros-1 proto-oncogene (ROS1), and hepatocyte growth factor receptor (MET) exon 14 alterations and early stage (IA-IIIA) NSCLC will be treated with induction EGFR tyrosine kinase inhibitor (TKI) or crizotinib, a TKI that inhibits ALK, ROS1, and MET...
June 8, 2016: Clinical Lung Cancer
Alexa B Schrock, Garrett M Frampton, James Suh, Zachary R Chalmers, Mark Rosenzweig, Rachel L Erlich, Balazs Halmos, Jonathan Goldman, Patrick Forde, Kurt Leuenberger, Nir Peled, Gregory P Kalemkerian, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Siraj M Ali, Sai-Hong Ignatius Ou
BACKGROUND: The hepatocyte growth factor receptor gene (MET) exon 14 skipping (METex14) has recently been described a potential driver alteration in lung cancer targetable by mesenchymal-to-epithelial transition factor (MET) tyrosine kinase inhibitors (TKIs). METHODS: Well-validated hybrid capture-based comprehensive genomic profiling was performed at the request of individual treating physicians. RESULTS: Of 11,205 lung cancers profiled by comprehensive genomic profiling, 298 (2...
September 2016: Journal of Thoracic Oncology
Rebecca S Heist, Lecia V Sequist, Darrell Borger, Justin F Gainor, Ronald S Arellano, Long P Le, Dora Dias-Santagata, Jeffrey W Clark, Jeffrey A Engelman, Alice T Shaw, A John Iafrate
INTRODUCTION: MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping is a targetable alteration in lung cancer. Treatment with MET proto-oncogene, receptor tyrosine kinase inhibitor can cause dramatic responses in patients whose cancers have MET exon 14 skipping. Little is known, however, about acquired resistance in patients with MET exon 14 skipping. METHODS: Biopsy specimens obtained at baseline and at the time of progression for a patient being treated with crizotinib were compared using targeted next-generation sequencing to assess for mechanisms of resistance...
August 2016: Journal of Thoracic Oncology
Si-Yang Liu, Lan-Ying Gou, An-Na Li, Na-Na Lou, Hong-Fei Gao, Jian Su, Jin-Ji Yang, Xu-Chao Zhang, Yang Shao, Zhong-Yi Dong, Qing Zhou, Wen-Zhao Zhong, Yi-Long Wu
INTRODUCTION: Predictive biomarkers of mesenchymal-to-epithelial transition factor (MET)-targeted therapy remain elusive. Since the discovery of the MNNG HOS Transforming gene (MET) exon 14 mutation, it has been found to have the best potential to become one precise biomarker for MET-targeted therapy. Here, we present the unique characteristics of MET exon 14 mutations in Chinese patients with NSCLC. METHODS: A total of 1296 patients with NSCLC were screened for MET exon 14 mutations...
September 2016: Journal of Thoracic Oncology
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