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Driver mutation lung cancer

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https://www.readbyqxmd.com/read/29780628/comprehensive-targeted-super-deep-next-generation-sequencing-enhances-differential-diagnosis-of-solitary-pulmonary-nodules
#1
Mingzhi Ye, Shiyong Li, Weizhe Huang, Chunli Wang, Liping Liu, Jun Liu, Jilong Liu, Hui Pan, Qiuhua Deng, Hailing Tang, Long Jiang, Weizhe Huang, Xi Chen, Di Shao, Zhiyu Peng, Renhua Wu, Jing Zhong, Zhe Wang, Xiaoping Zhang, Karsten Kristiansen, Jian Wang, Ye Yin, Mao Mao, Jianxing He, Wenhua Liang
Background: A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed. Methods: Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach. Results: Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29780256/the-utilization-of-next-generation-sequencing-to-detect-somatic-mutations-and-predict-clinical-prognosis-of-chinese-non-small-cell-lung-cancer-patients
#2
Liming Cao, Long Long, Min Li, Huaping Yang, Pengbo Deng, Xinru Mao, Jianxing Xiang, Bing Li, Tengfei Zhang, Chengping Hu
Purpose: The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods: We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#3
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#4
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29760833/synchronous-presence-of-egfr-alk-driver-mutations-along-with-pd-l1-overexpression-in-a-resected-early-stage-non-small-cell-lung-cancer-a-case-report-and-review-of-literature
#5
Nishitha Thumallapally, Sara Parylo, Adarsh Vennepureddy, Uroosa Ibrahim, Alisa Sokoloff
Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29755104/-multidisciplinary-approach-to-recurrence-after-resection-of-primary-lung-cancer
#6
Mitsuhiro Kamiyoshihara, Hitoshi Igai, Takashi Ibe, Fumi Ohsawa, Ryohei Yoshikawa, Kimihiro Shimizu, Akira Mogi, Ken Shirabe, Hiroyuki Kuwano
BACKGROUND: The standard approach for treating recurrence after complete resection of primary non-small cell lung cancer has been controversial. We present here a multidisciplinary strategy for postoperative recurrence in patients with primary lung cancer. PATIENTS AND METHODS: Over the last 7 years, we examined the disease-free survival and overall survival of 70 patients who underwent multidisciplinary treatment for recurrence after surgical resection of primary lung cancer...
April 2018: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/29748209/tas6417-a-novel-epidermal-growth-factor-receptor-inhibitor-targeting-exon-20-insertion-mutations
#7
Shinichi Hasako, Miki Terasaka, Naomi Abe, Takao Uno, Hirokazu Ohsawa, Akihiro Hashimoto, Ryoto Fujita, Kenji Tanaka, Takashige Okayama, Renu Wadhwa, Kazutaka Miyadera, Yoshimi Aoyagi, Kazuhiko Yonekura, Kenichi Matsuo
Activating mutations in the epidermal growth factor receptor (EGFR) gene are important targets in cancer therapy because they are key drivers of non-small-cell lung cancer (NSCLC). Whereas almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy...
May 10, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29737033/clonally-related-primary-alk-rearranged-adenocarcinoma-and-associated-metastatic-lesions
#8
You-Cai Zhu, Yun-Te Deng, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Kai-Qi Du
ALK rearrangement is a driver gene in non-small cell lung cancer (NSCLC). ALK-positive tumors are sensitive to ALK-tyrosine kinase inhibitors (TKIs). The detection of key driver genes is crucial to enable personalized treatment. Different histomorphological patterns have different driver genes. Herein, we report the case of a 42-year-old male patient diagnosed with adenocarcinoma with different histomorphologies in the primary lung site (mucinous type) and lymph node metastasis (solid type), of the same genotype, both presenting with ALK rearrangement but negative for EGFR mutation...
May 8, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29725504/robust-genomic-copy-number-predictor-of-pan-cancer-metastasis
#9
Alexander Pearlman, Kinnari Upadhyay, Kim Cole, John Loke, Katherine Sun, Susan Fineberg, Stephen J Freedland, Yongzhao Shao, Harry Ostrer
Copy number alterations(CNAs) are the most common genetic changes observed in many cancers, reflecting the innate chromosomal instability of this disorder. Yet, how these alterations affect gene function to promote metastases across different tumor types has not been established. In this study, we developed a pan-cancer metastasis potential score (panMPS) based on observed CNAs. panMPS predicts metastasis and metastasis-free survival in cohorts of patients with prostate cancer, triple negative breast cancer and lung adenocarcinoma, and overall survival in the Metabric breast cancer cohort and three cohorts from The Cancer Genome Atlas (TCGA), including prostate, breast and lung adenocarcinoma...
January 2018: Genes & Cancer
https://www.readbyqxmd.com/read/29721196/comprehensive-genomic-transcriptomic-tumor-normal-gene-panel-analysis-for-enhanced-precision-in-patients-with-lung-cancer
#10
Shahrooz Rabizadeh, Chad Garner, John Zachary Sanborn, Stephen C Benz, Sandeep Reddy, Patrick Soon-Shiong
A CMS approved test for lung cancer is based on tumor-only analysis of a targeted 35 gene panel, specifically excluding the use of the patient's normal germline tissue. However, this tumor-only approach increases the risk of mistakenly identifying germline single nucleotide polymorphisms (SNPs) as somatically-derived cancer driver mutations (false positives). 621 patients with 30 different cancer types, including lung cancer, were studied to compare the precision of tumor somatic variant calling in 35 genes using tumor-only DNA sequencing versus tumor-normal DNA plus RNA sequencing...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721166/isolated-metastasis-of-an-egfr-l858r-mutated-nsclc-of-the-meninges-the-potential-impact-of-cxcl12-cxcr4-axis-in-egfr-mut-nsclc-in-diagnosis-follow-up-and-treatment
#11
Florian Lüke, Raquel Blazquez, Rezan Fahrioglu Yamaci, Xin Lu, Benedikt Pregler, Stefan Hannus, Karin Menhart, Dirk Hellwig, Hans-Jürgen Wester, Saskia Kropf, Daniel Heudobler, Jirka Grosse, Jutta Moosbauer, Markus Hutterer, Peter Hau, Markus J Riemenschneider, Michaela Bayerlová, Annalen Bleckmann, Bernhard Polzer, Tim Beißbarth, Christoph A Klein, Tobias Pukrop
Brain and leptomeningeal metastasis (LMM) of non-small cell lung cancer is still associated with poor prognosis. Moreover, the current diagnostic standard for LMM often yields false negative results and the scientific progress in this field is still unsatisfying. We present a case of a 71-year old patient with an isolated LMM. While standard diagnostics could only diagnose a cancer of unknown primary, the use of [68 Ga]-Pentixafor-PET/CT (CXCR4-PET/CT, a radiotracer targeting CXCR4) and a liquid biopsy of the cerebrospinal fluid revealed the primary NSCLC...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719623/validation-and-comparison-of-two-ngs-assays-for-the-detection-of-egfr-t790m-resistance-mutation-in-liquid-biopsies-of-nsclc-patients
#12
Claudia Vollbrecht, Annika Lehmann, Dido Lenze, Michael Hummel
Analysis of circulating cell-free DNA (cfDNA) derived from peripheral blood ("liquid biopsy") is an attractive alternative to identify non-small cell lung cancer (NSCLC) patients with the EGFR T790M mutation eligible for 3rd generation tyrosine kinase inhibitor therapy. We evaluated two PCR-based next generation sequencing (NGS) approaches, one including unique molecular identifiers (UMI), with focus on highly sensitive EGFR T790M mutation detection. Therefore, we extracted and sequenced cfDNA from synthetic plasma samples spiked with mutated DNA at decreasing allele frequencies and from 21 diagnostic NSCLC patients...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29717445/monitoring-of-response-and-resistance-in-plasma-of-egfr-mutant-lung-cancer-using-droplet-digital-pcr
#13
Yanan Kuang, Allison O'Connell, Adrian G Sacher, Nora Feeney, Ryan S Alden, Geoffrey R Oxnard, Cloud P Paweletz
The identification of oncogenic driver mutations has led to the rapid rise of genotype-directed treatments. However, genetic analysis of tumors remains cumbersome and a morbid experience for patients. Noninvasive assessment of tumor genotype, so-called "liquid biopsy," such as plasma genotyping represents a potentially transformative tool. Here we describe a genotyping protocol of cell-free plasma DNA (cfDNA) using Droplet Digital™ PCR (ddPCR™). ddPCR emulsifies DNA into ~20,000 droplets in which PCR is performed to endpoint in each droplet for both mutant and wild-type DNA...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29713584/pd-l1-testing-using-the-clone-22c3-pharmdx-kit-for-selection-of-patients-with-non-small-cell-lung-cancer-to-receive-immune-checkpoint-inhibitor-therapy-are-cytology-cell-blocks-a-viable-option
#14
Vanda F Torous, Deepa Rangachari, Benjamin P Gallant, Meghan Shea, Daniel B Costa, Paul A VanderLaan
Introduction: Programmed death ligand 1 (PD-L1) testing of non-small cell lung cancer (NSCLC) specimens helps select patients most likely to respond to immune checkpoint inhibitors. PD-L1 immunohistochemical testing is approved for formalin-fixed, paraffin-embedded (FFPE) surgical pathology specimens; however, the testing performance on FFPE cytology cell block specimens is unknown. Materials and Methods: The study is a retrospective cohort analysis of advanced stage NSCLC patients treated at our institution where tumor PD-L1 expression using the clone 22C3 pharmDx kit on the Dako Automated Link 48 platform was performed on either cytology cell block or surgical pathology specimens...
May 2018: Journal of the American Society of Cytopathology
https://www.readbyqxmd.com/read/29703472/single-cell-coagulomes-as-constituents-of-the-oncogene-driven-coagulant-phenotype-in-brain-tumours
#15
Nadim Tawil, Shilpa Chennakrishnaiah, Rayhaan Bassawon, Radia Johnson, Esterina D'Asti, Janusz Rak
Molecular profiling of human cancers revealed a startling diversity in disease-causing mechanisms superseding histological and anatomical commonalities. The emerging molecular subtypes and disease entities are often driven by distinct oncogenic pathways and their effectors, including those acting extracellularly on the vascular and coagulation systems. Indeed, several oncogenic mutations such as those affecting protein-coding genes (RAS, EGFR, PTEN, TP53) and non-coding RNA (microRNA) regulate multiple effectors of the coagulation system (coagulome), including tissue factor, protease activated receptors, clotting factors, mediators of platelet function and fibrinolysis...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29702285/brief-report-afatinib-and-cetuximab-in-four-patients-with-egfr-exon-20-insertion-positive-advanced-non-small-cell-lung-cancer
#16
Bianca van Veggel, Adrianus J de Langen, Sayed Hashemi, Kim Monkhorst, Daniëlle A M Heideman, Erik Thunnissen, Egbert F Smit
INTRODUCTION: Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-9% of EGFR mutated non-small-cell lung cancer (NSCLC). Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses. METHODS: Four patients with EGFR exon 20 insertion positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250-500 mg/m2 every two weeks...
April 24, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29697365/population-based-statistical-inference-for-temporal-sequence-of-somatic-mutations-in-cancer-genomes
#17
Je-Keun Rhee, Tae-Min Kim
BACKGROUND: It is well recognized that accumulation of somatic mutations in cancer genomes plays a role in carcinogenesis; however, the temporal sequence and evolutionary relationship of somatic mutations remain largely unknown. METHODS: In this study, we built a population-based statistical framework to infer the temporal sequence of acquisition of somatic mutations. Using the model, we analyzed the mutation profiles of 1954 tumor specimens across eight tumor types...
April 20, 2018: BMC Medical Genomics
https://www.readbyqxmd.com/read/29696132/brain-metastases-in-oncogene-addicted-non-small-cell-lung-cancer-patients-incidence-and-treatment
#18
REVIEW
J Remon, Benjamin Besse
Brain metastases (BM) are common in non-small cell lung cancer patients including in molecularly selected populations, such as EGFR -mutant and ALK -rearranged tumors. They are associated with a reduced quality of life, and are commonly the first site of progression for patients receiving tyrosine kinase inhibitors (TKIs). In this review, we summarize incidence of BM and intracranial efficacy with TKI agents according to oncogene driver mutations, focusing on important clinical issues, notably optimal first-line treatment in oncogene-addicted lung tumors with upfront BM (local therapies followed by TKI vs...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29690599/clinicopathological-characteristics-and-mutations-driving-development-of-early-lung-adenocarcinoma-tumor-initiation-and-progression
#19
REVIEW
Kentaro Inamura
Lung cancer is the leading cause of cancer-related deaths worldwide, with lung adenocarcinoma representing the most common lung cancer subtype. Among all lung adenocarcinomas, the most prevalent subset develops via tumorigenesis and progression from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to minimally invasive adenocarcinoma (MIA), to overt invasive adenocarcinoma with a lepidic pattern. This stepwise development is supported by the clinicopathological and molecular characteristics of these tumors...
April 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29683890/characteristics-and-predictive-value-of-pd-l1-status-in-real-world-non-small-cell-lung-cancer-patients
#20
Jeng-Sen Tseng, Tsung-Ying Yang, Chih-Ying Wu, Wen-Hui Ku, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang
Immunotherapy targeting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway has emerged as an effective treatment for lung cancer patients. It is important to evaluate the practicality of PD-L1 testing in real-world practice. A total of 211 non-small cell lung cancer patients were enrolled to detect 5 driver mutations and PD-L1 status (22C3 and SP263 assays) and to evaluate the characteristics of PD-L1 expression and its predictive value of immunotherapy. The PD-L1 positive (≥1%) and strong positive (≥50%) rate by SP263 assay was 27...
April 20, 2018: Journal of Immunotherapy
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