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Next generation sequencing AND lung cancer

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https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#1
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198463/overexpression-of-fam83h-as1-indicates-poor-patient-survival-and-knockdown-impairs-cell-proliferation-and-invasion-via-met-egfr-signaling-in-lung-cancer
#2
Jie Zhang, Shumei Feng, Wenmei Su, Shengbin Bai, Lei Xiao, Lihui Wang, Dafydd G Thomas, Jules Lin, Rishindra M Reddy, Philip W Carrott, William R Lynch, Andrew C Chang, David G Beer, You-Min Guo, Guoan Chen
Whole transcriptome analyses of next generation RNA sequencing (RNA-Seq) data from human cancer samples reveled thousands of uncharacterized non-coding RNAs including long non-coding RNA (lncRNA). Recent studies indicated that lncRNAs are emerging as crucial regulators in cancer processes and potentially useful as biomarkers for cancer diagnosis and prognosis. To delineate dysregulated lncRNAs in lung cancer, we analyzed RNA-Seq data from 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues. FAM83H-AS1, one of the top dysregulated lncRNAs, was found to be overexpressed in tumors relative to normal lung and significantly associated with worse patient survival in LUAD...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196074/clinical-applicability-and-cost-of-a-46-gene-panel-for-genomic-analysis-of-solid-tumours-retrospective-validation-and-prospective-audit-in-the-uk-national-health-service
#3
Angela Hamblin, Sarah Wordsworth, Jilles M Fermont, Suzanne Page, Kulvinder Kaur, Carme Camps, Pamela Kaisaki, Avinash Gupta, Denis Talbot, Mark Middleton, Shirley Henderson, Anthony Cutts, Dimitrios V Vavoulis, Nick Housby, Ian Tomlinson, Jenny C Taylor, Anna Schuh
BACKGROUND: Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28182994/atm-deficient-colorectal-cancer-cells-are-sensitive-to-the-parp-inhibitor-olaparib
#4
Chen Wang, Nicholas Jette, Daniel Moussienko, D Gwyn Bebb, Susan P Lees-Miller
The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors...
February 6, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28170370/development-of-a-gene-panel-for-next-generation-sequencing-of-clinically-relevant-mutations-in-cell-free-dna-from-cancer-patients
#5
Umberto Malapelle, Clara Mayo de-Las-Casas, Danilo Rocco, Monica Garzon, Pasquale Pisapia, Nuria Jordana-Ariza, Maria Russo, Roberta Sgariglia, Caterina De Luca, Francesco Pepe, Alejandro Martinez-Bueno, Daniela Morales-Espinosa, María González-Cao, Niki Karachaliou, Santiago Viteri Ramirez, Claudio Bellevicine, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone
BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma...
February 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28167215/treatments-for-egfr-mutant-non-small-cell-lung-cancer-nsclc-the-road-to-a-success-paved-with-failures
#6
REVIEW
Dae Ho Lee
The discovery of epidermal growth factor receptor (EGFR) activating mutations in non-small cell lung cancer (NSCLC) and the success story of EGFR tyrosine kinases inhibitors (TKIs) has changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. As a result, EGFR TKI therapy, including gefitinib, erlotinib and afatinib, has become the standard therapy for NSCLC patients with EGFR activating mutation as first-line therapy. However, most patients inevitably progress despite initial dramatic and rapid response to EGFR TKIs and therefore during the last decade, a lot of efforts have been made to identify and overcome various resistance mechanisms...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28154808/patient-derived-xenograft-models-of-non-small-cell-lung-cancer-and-their-potential-utility-in-personalized-medicine
#7
Katherine M Morgan, Gregory M Riedlinger, Jeffrey Rosenfeld, Shridar Ganesan, Sharon R Pine
Traditional preclinical studies of cancer therapeutics have relied on the use of established human cell lines that have been adapted to grow in the laboratory and, therefore, may deviate from the cancer they were meant to represent. With the emphasis of cancer drug development shifting from non-specific cytotoxic agents to rationally designed molecularly targeted therapies or immunotherapy comes the need for better models with predictive value regarding therapeutic activity and response in clinical trials. Recently, the diversity and accessibility of immunodeficient mouse strains has greatly enhanced the production and utility of patient-derived xenograft (PDX) models for many tumor types, including non-small cell lung cancer (NSCLC)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28153953/evaluation-of-a-fast-and-fully-automated-platform-to-diagnose-egfr-and-kras-mutations-in-formalin-fixed-and-paraffin-embedded-non-small-cell-lung-cancer-samples-in-less-than-one-day
#8
Laetitia Lambros, Charline Caumont, Briac Guibourg, Fanny Barel, Isabelle Quintin-Roué, Pascale Marcorelles, Jean-Philippe Merlio, Arnaud Uguen
AIMS: Searching for EGFR and KRAS mutations within non-small cell lung carcinoma (NSCLC) samples remains time-consuming and can delay treatment choices in patients with acute deterioration. We evaluated the performances of the fully automated Idylla platform to quickly detect these mutations in NSCLC samples. METHODS: We used the Idylla EGFR Mutation Assay and the Idylla KRAS Mutation Test to analyse 18 formalin-fixed paraffin-embedded NSCLC tumour samples with known EGFR and KRAS mutation status according to next-generation sequencing (NGS) and droplet digital PCR (ddPCR) for EGFRT790M mutations...
February 2, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28152008/highly-sensitive-detection-of-a-her2-12-base-pair-duplicated-insertion-mutation-in-lung-cancer-using-the-eprobe-pcr-method
#9
Yoshiaki Takase, Kengo Usui, Kimihiro Shimizu, Yasumasa Kimura, Tatsuo Ichihara, Takahiro Ohkawa, Jun Atsumi, Yasuaki Enokida, Seshiru Nakazawa, Kai Obayashi, Yoichi Ohtaki, Toshiteru Nagashima, Yasumasa Mitani, Izumi Takeyoshi
Somatic mutation in human epidermal growth factor receptor-related 2 gene (HER2) is one of the driver mutations in lung cancer. HER2 mutations are found in about 2% of lung adenocarcinomas (ADCs). Previous reports have been based mainly on diagnostic screening by Sanger sequencing or next-generation sequencing (NGS); however, these methods are time-consuming and complicated. We developed a rapid, simple, sensitive mutation detection assay for detecting HER2 12 base pair-duplicated insertion mutation based on the Eprobe-mediated PCR method (Eprobe-PCR) and validated the sensitivity of this assay system for clinical diagnostics...
2017: PloS One
https://www.readbyqxmd.com/read/28144970/pulmonary-adenocarcinoma-with-epidermal-growth-factor-receptor-mutations-in-asbestos-exposed-non-smokers-a-case-series
#10
Richard L Kradin, John Iafrate, David C Christiani
BACKGROUND: Cigarette smoke and asbestos are recognized causes of lung carcinoma and together promote carcinogenesis. Adenocarcinoma is currently the most common cause of lung cancer in the USA and it has been linked to both smoking and asbestos exposure. Mutations in the epidermal growth factor gene receptor (EGFR) occur predominantly in non-smokers with adenocarcinoma. Methods Mutations in the EGFR gene were investigated using next-generation sequencing. RESULTS: We report the presence of EGFR exon point mutations in the pulmonary adenocarcinomas of three never-smokers occupationally exposed to asbestos...
February 1, 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28103826/tracking-the-origin-of-simultaneous-endometrial-and-ovarian-cancer-by-next-generation-sequencing-a-case-report
#11
Nadejda Valtcheva, Franziska M Lang, Aurelia Noske, Eleftherios P Samartzis, Anna-Maria Schmidt, Elisa Bellini, Daniel Fink, Holger Moch, Markus Rechsteiner, Konstantin J Dedes, Peter J Wild
BACKGROUND: Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. CASE PRESENTATION: In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary...
January 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in%C3%A2-advanced-nsclc
#12
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
No abstract text is available yet for this article.
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#13
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing. METHODS: Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#14
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28065930/rapid-changes-in-circulating-tumor-dna-in-serially-sampled-plasma-during-treatment-of-breast-cancer-a-case-report
#15
Hiroshi Nakagomi, Yosuke Hirotsu, Kenji Amemiya, Haruka Nakada, Masayuki Inoue, Hitoshi Mochizuki, Toshio Oyama, Masao Omata
BACKGROUND The analysis of circulating tumor DNA (ctDNA) is expected to be a modality to determine the status of cancer in real time. This case indicated utilities and issues in measuring the ctDNA in cancer patients. CASE REPORT A 45-year-old woman with metastatic breast cancer was treated with bevacizumab and paclitaxel. The lung metastases were decreased but the meningitis carcinoma developed rapidly and she died. During the treatment with bevacizumab and paclitaxel, blood samples were taken serially and ctDNA was analyzed using a next-generation sequencer...
January 9, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28028034/rapamycin-insensitive-companion-of-mtor-rictor-amplification-defines-a-subset-of-advanced-gastric-cancer-and-is-sensitive-to-azd2014-mediated-mtorc1-2-inhibition
#16
S T Kim, S Y Kim, S J Klempner, J Yoon, N Kim, S Ahn, H Bang, K-M Kim, W Park, S H Park, J O Park, Y S Park, H Y Lim, S H Lee, K Park, W K Kang, J Lee
PURPOSE: Targeting oncogenic genomic aberrations is an established therapeutic strategy in multiple tumor types. Molecular classification has uncovered a number of novel targets, and rapamycin-insensitive companion of mTOR (RICTOR) amplification has been identified in lung cancer. Further investigation assessing the therapeutic potential of RICTOR amplification as a novel target across advanced cancers is needed. PATIENTS AND METHODS: Tumor samples from 640 patients with metastatic solid tumors, primarily gastrointestinal and lung cancers were prospectively subjected to a next-generation sequencing (NGS) assay to identify molecular targets...
December 27, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28027313/base-position-error-rate-analysis-of-next-generation-sequencing-applied-to-circulating-tumor-dna-in-non-small-cell-lung-cancer-a-prospective-study
#17
Nicolas Pécuchet, Eleonora Zonta, Audrey Didelot, Pierre Combe, Constance Thibault, Laure Gibault, Camille Lours, Yves Rozenholc, Valérie Taly, Pierre Laurent-Puig, Hélène Blons, Elizabeth Fabre
BACKGROUND: Circulating tumor DNA (ctDNA) is an approved noninvasive biomarker to test for the presence of EGFR mutations at diagnosis or recurrence of lung cancer. However, studies evaluating ctDNA as a noninvasive "real-time" biomarker to provide prognostic and predictive information in treatment monitoring have given inconsistent results, mainly due to methodological differences. We have recently validated a next-generation sequencing (NGS) approach to detect ctDNA. Using this new approach, we evaluated the clinical usefulness of ctDNA monitoring in a prospective observational series of patients with non-small cell lung cancer (NSCLC)...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28000891/expression-of-mir%C3%A2-26a-exhibits-a-negative-correlation-with-hmga1-and-regulates-cancer-progression-by-targeting-hmga1-in-lung-adenocarcinoma-cells
#18
Noboru Sekimoto, Ayako Suzuki, Yutaka Suzuki, Sumio Sugano
Lung cancer is the most common cause of cancer‑associated mortality worldwide, and the number of cases is increasing annually. Several studies have shown that microRNAs (miRNAs) control proliferation, differentiation, and apoptosis in various cell types, and increasing evidence indicates the presence of aberrant miRNA expression profiles and unique miRNA signaling pathways in several types of cancer. The present study aimed to identify miRNAs, which correlated specifically with the progression of lung cancer through the analysis of 57,100 transcripts and 1,341 small RNA expression profiles in 26 lung adenocarcinoma cell lines using next‑generation sequencing...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27994651/massive-parallel-sequencing-and-digital-gene-expression-analysis-reveals-potential-mechanisms-to-overcome-therapy-resistance-in-pulmonary-neuroendocrine-tumors
#19
Robert Fred Henry Walter, Claudia Vollbrecht, Daniel Christoph, Robert Werner, Jan Schmeller, Elena Flom, Georgia Trakada, Aggeliki Rapti, Vasilis Adamidis, Wolfgang Hohenforst-Schmidt, Jens Kollmeier, Thomas Mairinger, Jeremias Wohlschlaeger, Paul Zarogoulidis, Konstantinos Porpodis, Kurt Werner Schmidt, Fabian Dominik Mairinger
Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27987594/characterization-of-microbiome-in-bronchoalveolar-lavage-fluid-of-patients-with-lung-cancer-comparing-with-benign-mass-like-lesions
#20
Sang Hoon Lee, Ji Yeon Sung, Dongeun Yong, Jongsik Chun, Song Yee Kim, Joo Han Song, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Se Kyu Kim, Joon Chang, Moo Suk Park
OBJECTIVES: Disruption in the stability of respiratory microbiota is known to be associated with many chronic respiratory diseases. However, only few studies have examined microbiomes in lung cancer. Therefore, we characterized and compared the microbiomes of patients with lung cancer and those with benign mass-like lesions. MATERIALS AND METHODS: Bronchoalveolar fluid was collected prospectively to evaluate lung masses in patients who had undergone bronchoscopies from May to September 2015...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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