met exon 14

AIMS: Gastrointestinal stromal tumors (GISTs) may arise anywhere in the gastrointestinal tract, but are rare in the esophagus. We describe the clinical, pathologic, and molecular characteristics of 27 primary esophageal 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. Esophageal GISTs occurred in 14 men and 13 women between 22 and 80 years of age (mean, 56 years)...

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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...

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...

Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METΔ14). Here we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METΔ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a Hepatocyte growth factor (HGF)-dependent manner...

Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...

INTRODUCTION: Response to MET inhibitors in non-small cell lung cancer with MET exon 14 (METex14) skipping has fueled molecular screening efforts and search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping METHODS: Among 795 East-Asian patients who underwent surgery for non-small cell lung cancer, we screened 45 patients with quintuple-negative (EGFR-/KRAS-/ALK-/ROS1-/RET-) lung adenocarcinomas using RT-PCR, and found 17 patients (37...

Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1)...

Background: Pulmonary sarcomatoid carcinoma (SC) is a rare disease with poor prognosis and with strong inter- and intratumor heterogeneity. However, molecular classification is currently focused on activating MET mutations. We sought to better characterize the molecular diversity of SC using mutational signatures that reflect different mutational processes, such as tobacco-associated adducts (signature 4), BRCA1/BRCA2 deficiency (signature 3) or APOBEC enzyme deamination (signatures 2&13)...

MET exon 14 splicing mutations are new targetable oncogenic drivers reported in 3% of non-small cell lung cancer (NSCLC) cases and have been shown to be more common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian patients, with a large adenocarcinoma cohort as internal control.We tested 81 patients with SC and 150 with adenocarcinoma for splice site DNA mutations leading to RNA splicing-based skipping of MET exon 14...

BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation...

The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL), which is mostly seen in immunosuppressed patients. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated in PEL cells and represents a promising therapeutic target (Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET activation within PEL cells remain largely unknown...

Inhibitors of the receptor tyrosine kinase (RTK) MET have been ineffective at treating cancer, possibly because of lack of knowledge that would allow selection of tumors likely to respond to this treatment. In contrast, specific epidermal growth factor receptor (EGFR) inhibitors have been used successfully against lung tumors displaying activating mutations in the kinase domain of EGFR. Recent publications describe a set of mutations causing MET exon 14 skipping, and importantly, several case reports describe objective responses to MET-targeting tyrosine kinase inhibitors in patients with such mutations...

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization. METHODS: Hybrid capture-based comprehensive genomic profiling was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1...

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...

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...

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...

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...

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...

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...