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met exon 14

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https://www.readbyqxmd.com/read/29217198/clinical-molecular-and-computational-analysis-in-two-cases-with-mitochondrial-encephalomyopathy-associated-with-suclg1-mutation-in-a-consanguineous-family
#1
Marwa Maalej, Amel Tej, Jihène Bouguila, Samia Tilouche, Senda Majdoub, Boudour Khabou, Mouna Tabbebi, Rahma Felhi, Marwa Ammar, Emna Mkaouar-Rebai, Leila Keskes, Lamia Boughamoura, Faiza Fakhfakh
Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (β subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29188469/met-targeting-antibody-emibetuzumab-and-kinase-inhibitor-merestinib-as-single-agent-or-in-combination-in-a-cancer-model-bearing-met-exon-14-skipping
#2
S Betty Yan, Suzane L Um, Victoria L Peek, Jennifer R Stephens, Wei Zeng, Bruce W Konicek, Ling Liu, Jason R Manro, Volker Wacheck, Richard A Walgren
Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14 skipping, an oncogenic driver which is further evidenced by case reports of patient response to MET kinase inhibitor treatment. Approximately 15% of tumors harboring MET exon14 skipping have concurrent MET amplification. Experimental Design Merestinib is a type II MET kinase inhibitor. Emibetuzumab, a bivalent anti-MET antibody, internalizes MET receptor. Each single agent and the combination were evaluated in the Hs746t gastric cancer line bearing MET exon14 skipping and MET amplification...
November 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29139039/genetic-screening-and-molecular-characterization-of-met-alterations-in-non-small-cell-lung-cancer
#3
M Saigi, A McLeer-Florin, E Pros, E Nadal, E Brambilla, M Sanchez-Cespedes
PURPOSE: Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery. METHODS AND PATIENTS: 157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations...
November 14, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29066084/comparative-genomic-profiling-of-matched-primary-and-metastatic-tumors-in-renal-cell-carcinoma
#4
Maria F Becerra, Ed Reznik, Almedina Redzematovic, Daniel M Tennenbaum, Mahyar Kashan, Mazyar Ghanaat, Jozefina Casuscelli, Brandon Manley, Philip Jonsson, Renzo G DiNatale, Kyle A Blum, Jeremy C Durack, Stephen B Solomon, Maria E Arcila, Caitlin Bourque, Nick Socci, Maria I Carlo, Chung-Han Lee, Martin H Voss, Darren R Feldman, Robert J Motzer, Jonathan A Coleman, Paul Russo, Emily H Cheng, A Ari Hakimi, James J Hsieh
BACKGROUND: Next-generation sequencing (NGS) studies of matched pairs of primary and metastatic tumors in renal cell carcinoma (RCC) have been limited to small cohorts. OBJECTIVE: To evaluate the discordance in somatic mutations between matched primary and metastatic RCC tumors. DESIGN, SETTING, AND PARTICIPANTS: Primary tumor (P), metastasis (M), and germline DNA from 60 patients with RCC was subjected to NGS with a targeted exon capture-based assay of 341 cancer-associated genes...
October 20, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29063069/targeting-met-in-cancer-therapy
#5
REVIEW
Hong-Nan Mo, Peng Liu
MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile...
September 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29037218/clinicopathologic-features-and-treatment-efficacy-of-chinese-patients-with-braf-mutated-metastatic-colorectal-cancer-a-retrospective-observational-study
#6
Xicheng Wang, Qing Wei, Jing Gao, Jian Li, Jie Li, Jifang Gong, Yanyan Li, Lin Shen
BACKGROUND: The prognostic role of the V600E mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs. METHODS: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute (Beijing, China) between July 2011 and July 2016...
October 16, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28960774/the-bdnf-val66met-polymorphism-is-associated-with-lower-bmi-lower-postprandial-glucose-levels-and-elevated-carbohydrate-intake-in-children-and-adolescents
#7
A Kalenda, K Landgraf, D Löffler, P Kovacs, W Kiess, A Körner
BACKGROUND: The amino acid-changing exonic variant rs6265 (Val66Met polymorphism) in the brain-derived neurotrophic factor (BDNF) has been linked to obesity in several genotype-phenotype association studies. OBJECTIVE: To identify metabolic factors by which this effect might be conveyed, we aimed to investigate its correlation with (i) obesity, (ii) metabolic parameters, (iii) serum levels of BDNF and (iv) measures of energy intake in children and adolescents. METHODS: We genotyped the variant in 2131 subjects (age 6-18 years) and checked for an association with obesity...
September 27, 2017: Pediatric Obesity
https://www.readbyqxmd.com/read/28958502/dacomitinib-versus-gefitinib-as-first-line-treatment-for-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-archer-1050-a-randomised-open-label-phase-3-trial
#8
Yi-Long Wu, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Fumito Tsuji, Rolf Linke, Rafael Rosell, Jesus Corral, Maria Rita Migliorino, Adam Pluzanski, Eric I Sbar, Tao Wang, Jane Liang White, Sashi Nadanaciva, Rickard Sandin, Tony S Mok
BACKGROUND: Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC). METHODS: In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions...
September 25, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28952227/analysis-of-the-status-of-egfr-ros1-and-met-genes-in-non-small-cell-lung-adenocarcinoma
#9
Qiong Wang, Yali Lv, Mei Zhong, Fengwei Zhu, Lixin Wei, Huaiyin Shi
PURPOSE: To investigate the status and distribution of epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (MET), and receptor tyrosine kinase (ROS1) genes in patients with non-small cell lung (NSCL) adenocarcinoma. METHODS: The copy number of the MET gene was detected using fluorescence in situ hybridization (FISH). The splice mutation in exon 14 gene was detected by Sanger sequencing. The mutations in EGFR and the fusion of the ROS1 gene were detected using the fluorescence real-time quantitative PCR method (RT-qPCR)...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28943896/a-large-chinese-pedigree-of-multiple-endocrine-neoplasia-type-2a-with-a-novel-c634y-d707e-germline-mutation-in-ret-exon-11
#10
Fanqian Lu, Xiaohong Chen, Yunlong Bai, Yaru Feng, Jian Wu
The present study identified the clinical features of the largest multiple endocrine neoplasia type 2 (MEN2) A pedigree from China, with a novel double missense rearranged during transfection (RET) mutation (C634Y/D707E). To the best of our knowledge, the D707E mutation has not been identified to date. In the present study, a total of 101 family members who originated from a large pedigree (134 members in total) underwent RET mutation screening by next-generation sequencing and polymerase chain reaction (PCR) amplification, followed by direct bidirectional DNA sequencing...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28843992/tracking-met-de-addiction-in-lung-cancer-a-road-towards-the-oncogenic-target
#11
REVIEW
S Pilotto, L Carbognin, N Karachaliou, P C Ma, R Rosell, G Tortora, E Bria
The discovery of druggable oncogenic drivers (i.e. EGFR and ALK), along with the introduction of comprehensive tumor genotyping techniques into the daily clinical practice define non-small-cell lung cancer (NSCLC) asa group of heterogeneous diseases, requiring a context-personalized clinico-therapeutical approach. Among the most investigated biomarkers, the MET proto-oncogene has been extensively demonstrated to play a crucial role throughout the lung oncogenesis, unbalancing the proliferation/apoptosis signaling and influencing the epithelial-mesenchymal transition and the invasive phenotype...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28799536/estrogen-receptor-esr1-mutation-in-bone-metastases-from-breast-cancer
#12
Stephan Bartels, Matthias Christgen, Angelina Luft, Sascha Persing, Kai Jödecke, Ulrich Lehmann, Hans Kreipe
Activating mutations of estrogen receptor α gene (ESR1) in breast cancer can cause endocrine resistance of metastatic tumor cells. The skeleton belongs to the metastatic sides frequently affected by breast cancer. The prevalence of ESR1 mutation in bone metastasis and the corresponding phenotype are not known. In this study bone metastases from breast cancer (n=231) were analyzed for ESR1 mutation. In 27 patients (12%) (median age 73 years, range: 55-82 years) activating mutations of ESR1 were detected. The most frequent mutation was p...
August 11, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28779874/met-exon-14-alterations-and-new-resistance-mutations-to-tyrosine-kinase-inhibitors-risk-of-inadequate-detection-with-current-amplicon-based-ngs-panels
#13
Brigitte Poirot, Ludovic Doucet, Shirine Benhenda, Jérôme Champ, Véronique Meignin, Jacqueline Lehmann-Che
INTRODUCTION: Targeted therapies such as tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of lung adenocarcinoma, and detection of activating mutations of genes such as EGFR or anaplastic lymphoma kinase gene (ALK) is now mandatory in the clinical setting. However, additional targetable alterations are continuously being described and forcing us to adapt our detection methods. Here we have evaluated the ability of eight amplicon-based next-generation sequencing (NGS) panels to detect the recently described mesenchymal epithelial transition factor (MET) exon 14 (METex14) alterations or new mutations conferring resistance to TKIs...
October 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28765324/glesatinib-exhibits-antitumor-activity-in-lung-cancer-models-and-patients-harboring-met-exon-14-mutations-and-overcomes-mutation-mediated-resistance-to-type-i-met-inhibitors-in-nonclinical-models
#14
Lars D Engstrom, Ruth Aranda, Matthew Lee, Elizabeth A Tovar, Curt J Essenburg, Zachary Madaj, Harrah Chiang, David Briere, Jill Hallin, Pedro P Lopez-Casas, Natalia Baños, Camino Menendez, Manuel Hidalgo, Vanessa Tassell, Richard Chao, Darya I Chudova, Richard B Lanman, Peter Olson, Lyudmilla Bazhenova, Sandip Pravin Patel, Carrie Graveel, Mizuki Nishino, Geoffrey I Shapiro, Nir Peled, Mark M Awad, Pasi A Jänne, James G Christensen
Purpose:MET exon 14 deletion (METex14 del) mutations represent a novel class of non-small cell lung cancer (NSCLC) driver mutations. We evaluated glesatinib, a spectrum-selective MET inhibitor exhibiting a type II binding mode, in METex14 del-positive nonclinical models and NSCLC patients and assessed its ability to overcome resistance to type I MET inhibitors.Experimental Design: As most MET inhibitors in clinical development bind the active site with a type I binding mode, we investigated mechanisms of acquired resistance to each MET inhibitor class utilizing in vitro and in vivo models and in glesatinib clinical trials...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28743157/her2-mutations-in-lung-adenocarcinomas-a-report-from-the-lung-cancer-mutation-consortium
#15
Rathi N Pillai, Madhusmita Behera, Lynne D Berry, Mike R Rossi, Mark G Kris, Bruce E Johnson, Paul A Bunn, Suresh S Ramalingam, Fadlo R Khuri
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). METHODS: Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers...
November 1, 2017: Cancer
https://www.readbyqxmd.com/read/28679766/sym015-a-highly-efficacious-antibody-mixture-against-met-amplified-tumors
#16
Thomas Tuxen Poulsen, Michael Monrad Grandal, Niels Jørgen Østergaard Skartved, Rikke Hald, Lene Alifrangis, Klaus Koefoed, Trine Lindsted, Camilla Fröhlich, Sofie Ellebæk Pollmann, Karsten Wessel Eriksen, Anna Dahlman, Helle Jane Jacobsen, Thomas Bouquin, Mikkel Wandahl Pedersen, Ivan David Horak, Johan Lantto, Michael Kragh
Purpose: Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target MET more effectively, we developed an antagonistic antibody mixture, Sym015, consisting of two humanized mAbs directed against nonoverlapping epitopes of MET.Experimental Design/Results: We screened a large panel of well-annotated human cancer cell lines and identified a subset with highly elevated MET expression. In particular, cell lines of lung cancer and gastric cancer origin demonstrated high MET expression and activation, and Sym015 triggered degradation of MET and significantly inhibited growth of these cell lines...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28644569/gastrointestinal-stromal-tumours-of-the-oesophagus-a-clinicopathological-and-molecular-analysis-of-27-cases
#17
Guhyun Kang, Yuna Kang, Kyung-Hee Kim, Sang Yun Ha, Jung Yeon Kim, Young Mog Shim, Michael C Heinrich, Kyoung-Mee Kim, Christopher L Corless
AIMS: Gastrointestinal stromal tumours (GISTs) may arise anywhere in the gastrointestinal tract, but are rare in the oesophagus. We describe the clinical, pathological and molecular characteristics of 27 primary oesophageal GISTs, the largest series to date. METHODS AND RESULTS: DNA was extracted and exons 9, 11, 13 and 17 of KIT, exons 12, 14 and 18 of PDGFRA and exon 15 of BRAF were amplified and sequenced. Oesophageal GISTs occurred in 14 men and 13 women aged between 22 and 80 years (mean: 56 years)...
June 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28587017/case-series-of-met-exon-14-skipping-mutation-positive-non-small-cell-lung-cancers-and-response-to-crizotinib
#18
S X Wang, B Zhang, H A Wakelee, M Diehn, C Kunder, J W Neal
No abstract text is available yet for this article.
May 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28577945/systematic-identification-of-cancer-related-long-noncoding-rnas-and-aberrant-alternative-splicing-of-quintuple-negative-lung-adenocarcinoma-through-rna-seq
#19
Lu Zhang, Shiyong Li, Yoon-La Choi, Jinseon Lee, Zhuolin Gong, Xiaoqiao Liu, Yunfei Pei, Awei Jiang, Mingzhi Ye, Mao Mao, Xuegong Zhang, Jhingook Kim, Ronghua Chen
OBJECTIVES: Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer prevalent in Asia. There is a dearth of understanding regarding the transcriptome landscape of LUAD without primary known driver mutations. In this study, LUAD samples without well-known driver mutations occurring in EGFR, KRAS, ALK, ROS1 or RET (quintuple-negative) were used for transcriptome study with a focus on long noncoding RNAs (lncRNAs), alternative splicing and gene fusions. MATERIALS AND METHODS: 24 pairs of LUAD and adjacent normal samples and 13 tumor-only samples derived from 37 quintuple-negative patients were used...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28545270/-correlation-between-mutation-of-p53-gene-2-4-exons-from-peripheral-blood-and-hpv16-positive-cervical-cancer-susceptibility-and-clinical-significance
#20
C M Yin, Y F Yao, Z L Yan, H Y Yang
Objective: To detect mutations of p53 gene 2-4 exons from peripheral blood and to explore their relevance in HPV16-positive cervical cancer susceptibility and clinical significance. Methods: Collected firstly cases from the Third Affiliated Hospital of Kunming Medical University from October 2012 to April 2014, included 167 cases HPV16-postive cervical cancer and 160 cases HPV-negative healthy women. Genomic DNA from the host peripheral venous blood was taken, mutations of p53 gene 2-4 exons were analyzed with software DNAstar after PCR and bidirectional sequencing...
May 25, 2017: Zhonghua Fu Chan Ke za Zhi
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