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met exon 14

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https://www.readbyqxmd.com/read/28315738/pulmonary-sarcomatoid-carcinomas-commonly-harbor-either-potentially-targetable-genomic-alterations-or-high-tumor-mutational-burden-as-observed-by-comprehensive-genomic-profiling
#1
Alexa B Schrock, Shuyu D Li, Garrett M Frampton, James Suh, Eduardo Braun, Ranee Mehra, Steven Buck, Jose A Bufill, Nir Peled, Nagla Abdel Karim, Cynthia Hsieh, Manuel Doria, James Knost, Rong Chen, Sai-Hong Ignatius Ou, Jeffrey S Ross, Philip J Stephens, Paul Fishkin, Vincent A Miller, Siraj M Ali, Balazs Halmos, Jane J Liu
BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade non-small cell lung carcinoma (NSCLC) characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered due to limited and inconsistent molecular characterization. METHODS: Hybrid-capture based comprehensive genomic profiling (CGP) was performed on DNA from 15,867 FFPE NSCLCs including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1...
March 15, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28303491/changing-the-therapeutic-landscape-in-non-small-cell-lung-cancers-the-evolution-of-comprehensive-molecular-profiling-improves-access-to-therapy
#2
REVIEW
Joshua K Sabari, Fernando Santini, Isabella Bergagnini, W Victoria Lai, Kathryn C Arbour, Alexander Drilon
Targeting genomic alterations has led to a paradigm shift in the treatment of patients with lung cancer. In an effort to better identify potentially actionable alterations that may predict response to FDA-approved and or investigational therapies, many centers have migrated towards performing targeted exome sequencing in patients with stage IV disease. The implementation of next-generation sequencing (NGS) in the evaluation of tumor tissue from patients with NSCLC has led to the discovery of targetable alterations in tumors that previously had no known actionable targets by less comprehensive profiling...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28285687/met-exon-14-skipping-mutation-in-triple-negative-pulmonary-adenocarcinomas-and-pleomorphic-carcinomas-an-analysis-of-intratumoral-met-status-heterogeneity-and-clinicopathological-characteristics
#3
Dohee Kwon, Jaemoon Koh, Sehui Kim, Heounjeong Go, Young A Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Yoon Kyung Jeon, Doo Hyun Chung
OBJECTIVES: MET mutations leading to exon 14 skipping rarely occur in non-small cell lung cancer (NSCLC). Recently, small molecule inhibitors targeting MET mutations showed clinical benefit. However, the clinicopathological characteristics of NSCLC harboring MET mutations, and the correlation among mutations, protein expression, and gene copy number of MET in NSCLC remain unclear. Therefore, we address these issues. MATERIALS AND METHODS: MET exon 14 skipping mutations were evaluated using real-time quantitative reverse-transcription-PCR (qRT-PCR) in 102 triple-negative (i...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28271038/successful-crizotinib-monotherapy-in-egfr-mutant-lung-adenocarcinoma-with-acquired-met-amplification-after-erlotinib-therapy
#4
Katsuhiro Yoshimura, Naoki Inui, Masato Karayama, Yusuke Inoue, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Kengo Takeuchi, Haruhiko Sugimura, Takafumi Suda
MET is a driver oncogene in non-small-cell lung cancer (NSCLC), and its amplification is associated with acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A 56-year-old Japanese male with lung adenocarcinoma harboring an EGFR exon 21 L858R mutation received erlotinib to which he responded for 12 months. After disease progression, re-biopsy analyses revealed newly developed MET amplification. Neither EGFR exon 20 T790M mutation nor MET exon 14 mutations were detected...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28248723/performance-assessment-of-epidermal-growth-factor-receptor-gene-sequencing-according-to-sample-size-in-daily-practice-conditions
#5
Alejandro García, Constanza Lorente, María T Cuello, Mariana Dos Santos, Boris Elsner, Alejandra Avagnina, Valeria Denninghoff
Lung carcinoma is the main cause of cancer death worldwide. Adenocarcinoma molecular biomarkers have been discovered, and targeted therapies have been developed with encouraging results. The epidermal growth factor receptor gene is one of these biomarkers. Exons 18 to 21 should be studied in patients with advanced adenocarcinoma, who are candidates for treatment with tyrosine kinase inhibitors. The objective was to compare the performance of the determination in large and small samples in daily practice conditions, trying to adjust to published consensus guidelines...
February 28, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28218784/mutations-in-codons-12-and-13-of-k-ras-exon-2-in-colorectal-tumors-of-saudi-arabian-patients-frequency-clincopathological-associations-and-clinical-outcomes
#6
J Zekri, A Al-Shehri, M Mahrous, S Al-Rehaily, T Darwish, S Bassi, H El Taani, A Al Zahrani, S Elsamany, J Al-Maghrabi, B B Sadiq
Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28212996/analysis-of-a-panel-of-druggable-gene-mutations-and-of-alk-and-pd-l1-expression-in-a-series-of-thymic-epithelial-tumors-tets
#7
Marcello Tiseo, Angela Damato, Lucia Longo, Fausto Barbieri, Federica Bertolini, Alessandro Stefani, Mario Migaldi, Letizia Gnetti, Roberta Camisa, Paola Bordi, Sebastiano Buti, Giulio Rossi
INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consistent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETs aimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alpha and -beta, HER2 and c-MET) and the expression of ALK and PD-L1. PATIENTS AND METHODS: One hundred twelve consecutive cases of TETs and relative clinico-pathologic features were collected...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28169239/modified-mismatch-polymerase-chain-reaction-restriction-fragment-length-polymorphism-detected-mutations-in-codon-12-and-13-of-exon-2-of-k-ras-gene-in-colorectal-cancer-patients-and-its-association-with-liver-metastases-data-from-a-south-asian-country
#8
Fathima Dhilhani Mohamed Faleel, M I M De Zoysa, M D S Lokuhetti, Y I N S Gunawardena, Vishvanath Naduviladath Chandrasekharan, Ranil Samantha Dassanayake
AIM: Mutations in K-ras codon 12 and 13 of exon 2 are known to affect prognosis and impart resistance to anti-epidermal growth factor monoclonal antibody therapy in colorectal carcinoma (CRC). Our aim was to investigate the utility value of modified mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to detect mutation in K-ras codons of CRC patients and to relate the mutational status to liver metastasis. METHODOLOGY: Mismatch PCR-RFLP was developed to detect K-ras mutations in DNA isolated from paraffinized tumor tissue of thirty CRC patients...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28164087/met-exon-14-juxtamembrane-splicing-mutations-clinical-and-therapeutical-perspectives-for-cancer-therapy
#9
REVIEW
Sara Pilotto, Anastasios Gkountakos, Luisa Carbognin, Aldo Scarpa, Giampaolo Tortora, Emilio Bria
The MET proto-oncogene plays crucial roles in cell growth and proliferation, survival and apoptosis, epithelial-mesenchymal transition (EMT) and invasion, potentially conditioning the development and progression of the carcinogenesis process. The MET-associated aberrant signaling could be triggered by a variety of mechanisms, such as mutations, gene amplification, increased gene copy number and Met/HGF protein expression. Among the various MET alterations, MET exon 14 splicing abnormalities, causing the loss of the Met juxtamembrane (JM) domain, recently emerged as a new potential oncogenic driver and have been identified and validated across different cancer and histology subtypes...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28061541/a-prospective-multicenter-phase-ii-trial-of-low-dose-erlotinib-as-maintenance-treatment-after-platinum-doublet-chemotherapy-for-advanced-non-small-cell-lung-cancer-harboring-egfr-mutation
#10
Satoshi Hirano, Go Naka, Yuichiro Takeda, Motoyasu Iikura, Noriko Hayama, Asako Yanagisawa, Hiroyuki Amano, Makoto Nakamura, Sukeyuki Nakamura, Hiroshi Tabeta, Haruhito Sugiyama
BACKGROUND: Maintenance therapy with full-dose erlotinib for patients with advanced non-small cell lung cancer (NSCLC) has demonstrated a significant overall survival (OS) benefit. However, 150 mg/day of erlotinib seems too toxic as maintenance therapy. This study aimed to evaluate the efficacy and safety of low-dose erlotinib (25 mg/day) as maintenance treatment after platinum doublet chemotherapy in NSCLC harboring epidermal growth factor receptor (EGFR) mutation. METHODS: Activated EGFR-mutation-positive NSCLC patients who did not progress after first-line platinum-doublet chemotherapy, ≥20 and ≤85 years old, with performance status (PS) 0-3 were included in this study...
December 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28024701/a-comprehensive-analysis-of-clinical-outcomes-in-lung-cancer-patients-harboring-a-met-exon-14-skipping-mutation-compared-to-other-driver-mutations-in-an-east-asian-population
#11
Chien-Hung Gow, Min-Shu Hsieh, Shang-Gin Wu, Jin-Yuan Shih
INTRODUCTION: Recurrent somatic splice-site alterations at MET exon 14 (MET(Δ14)), which result in exon skipping and MET proto-oncogene, receptor tyrosine kinase (MET) activation, have been characterised. However, their demographic features and clinical outcomes in East Asian lung cancer patients have yet to be determined. METHODS: A one-step reverse transcription-polymerase chain reaction (RT-PCR), using RNA samples from 850 East Asian lung cancer patients, was performed in order to detect MET(Δ14) and five other major driver mutations, including those in the EGFR, KRAS, ALK, HER2, and ROS1 genes...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28024693/the-race-to-target-met-exon-14-skipping-alterations-in-non-small-cell-lung-cancer-the-why-the-how-the-who-the-unknown-and-the-inevitable
#12
REVIEW
Thanyanan Reungwetwattana, Ying Liang, Viola Zhu, Sai-Hong Ignatius Ou
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27988098/targeting-met-exon-14-skipping-alterations-has-lung-cancer-met-its-match
#13
EDITORIAL
Timothy A Yap, Sanjay Popat
No abstract text is available yet for this article.
January 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27987579/response-and-acquired-resistance-to-crizotinib-in-chinese-patients-with-lung-adenocarcinomas-harboring-met-exon-14-splicing-alternations
#14
Hua-Jie Dong, Peng Li, Chang-Ling Wu, Xiao-Yue Zhou, Hong-Jun Lu, Tong Zhou
Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to crizotinib in human lung adenocarcinomas. However, a substantial part of patients still has no sufficient tissue to perform genomic analysis. As a promising noninvasive biomarker and potential surrogate for the entire tumor genome, circulating tumor DNA (ctDNA) has been applied to the detection of driver gene mutations. Here we described the MET exon 14 splicing mutations in cell-free circulating-tumor DNA by next-generation sequencing (NGS) technology...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27969534/ps01-67-case-series-of-met-exon-14-skipping-mutation-positive-non-small-cell-lung-cancers-and-response-to-crizotinib-topic-medical-oncology
#15
Samantha X Wang, Bing M Zhang, Heather Wakelee, Maximilian Diehn, Christian A Kunder, Joel W Neal
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27928797/-changes-of-diagnosis-and-treatment-for-gastrointestinal-stromal-tumors-during-a-18-year-period-in-four-medical-centers-of-china
#16
Haibo Qiu, Peng Zhang, Xingyu Feng, Tao Chen, Xiaowei Sun, Jiang Yu, Zhijing Chen, Yong Li, Kaixiong Tao, Guoxin Li, Zhiwei Zhou
OBJECTIVE: To elucidate the historic and current diagnosis and treatment status of gastrointestinal stromal tumor (GIST) in the Chinese population based on four high volume databases. METHODS: Clinicopathological data of GIST patients with follow-up information between January 1998 and December 2015 from Sun Yat-sen University Cancer Center, Union Hospital of Huazhong University of Science and Technology, Southern Medical University Nanfang Hospital and Guangdong General Hospital were retrospectively analyzed...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#17
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
https://www.readbyqxmd.com/read/27864688/detection-of-mutations-in-the-braf-gene-in-patients-with-kit-and-pdgfra-wild-type-gastrointestinal-stromal-tumors
#18
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...
January 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27826534/fusion-gene-and-splice-variant-analyses-in-liquid-biopsies-of-lung-cancer-patients
#19
REVIEW
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
https://www.readbyqxmd.com/read/27794501/targeting-met-in-lung-cancer-will-expectations-finally-be-met
#20
REVIEW
Alexander Drilon, Federico Cappuzzo, Sai-Hong Ignatius Ou, D Ross Camidge
The hepatocyte growth factor receptor (MET) is a potential therapeutic target in a number of cancers, including NSCLC. In NSCLC, MET pathway activation is thought to occur through a diverse set of mechanisms that influence properties affecting cancer cell survival, growth, and invasiveness. Preclinical and clinical evidence suggests 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...
January 2017: Journal of Thoracic Oncology
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