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Next generation sequencing AND lung cancer

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https://www.readbyqxmd.com/read/28645111/intersecting-transcriptomic-profiling-technologies-and-long-non-coding-rna-function-in-lung-adenocarcinoma-discovery-mechanisms-and-therapeutic-applications
#1
REVIEW
Jonathan Castillo, Theresa R Stueve, Crystal N Marconett
Previously thought of as junk transcripts and pseudogene remnants, long non-coding RNAs (lncRNAs) have come into their own over the last decade as an essential component of cellular activity, regulating a plethora of functions within multicellular organisms. lncRNAs are now known to participate in development, cellular homeostasis, immunological processes, and the development of disease. With the advent of next generation sequencing technology, hundreds of thousands of lncRNAs have been identified. However, movement beyond mere discovery to the understanding of molecular processes has been stymied by the complicated genomic structure, tissue-restricted expression, and diverse regulatory roles lncRNAs play...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28639892/jak2-variations-and-functions-in-lung-adenocarcinoma
#2
Yanjun Xu, Juan Jin, Jiawei Xu, Yang W Shao, Yun Fan
Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers. Recently our study found that JAK2 might play an important role in lung cancer pathogenesis. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the variations and functions of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639239/significant-improvement-in-detecting-braf-kras-and-egfr-mutations-using-next-generation-sequencing-as-compared-with-fda-cleared-kits
#3
Wanlong Ma, Steven Brodie, Sally Agersborg, Vincent A Funari, Maher Albitar
INTRODUCTION: We compared mutations detected in EGFR, KRAS, and BRAF genes using next-generation sequencing (NGS) and confirmed by Sanger sequencing with mutations that could be detected by FDA-cleared testing kits. METHODS: Paraffin-embedded tissue from 822 patients was tested for mutations in EGFR, KRAS, and BRAF by NGS. Sanger sequencing of hot spots was used with locked nucleic acid to increase sensitivity for specific hot-spot mutations. This included 442 (54%) lung cancers, 168 (20%) colorectal cancers, 29 (4%) brain tumors, 33 (4%) melanomas, 14 (2%) thyroid cancers, and 16% others (pancreas, head and neck, and cancer of unknown origin)...
June 21, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28638459/towards-prognostic-profiling-of-non-small-cell-lung-cancer-new-perspectives-on-the-relevance-of-polo-like-kinase-1-expression-the-tp53-mutation-status-and-hypoxia
#4
Jolien Van den Bossche, Christophe Deben, Ken Op de Beeck, Vanessa Deschoolmeester, Christophe Hermans, Ines De Pauw, Julie Jacobs, Paul Van Schil, Jan Baptist Vermorken, Patrick Pauwels, Marc Peeters, Filip Lardon, An Wouters
Background: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required. Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division and the DNA damage response, is considered as a new potential biomarker in this research area...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28637487/the-nf1-somatic-mutational-landscape-in-sporadic-human-cancers
#5
REVIEW
Charlotte Philpott, Hannah Tovell, Ian M Frayling, David N Cooper, Meena Upadhyaya
BACKGROUND: Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia...
June 21, 2017: Human Genomics
https://www.readbyqxmd.com/read/28636540/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#6
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28625771/comparison-of-plasma-to-tissue-dna-mutations-in-surgical-patients-with-non-small-cell-lung-cancer
#7
Kezhong Chen, Jingbo Zhang, Tian Guan, Fan Yang, Feng Lou, Wei Chen, Mingyu Zhao, Jay Zhang, Siyi Chen, Jun Wang
OBJECTIVE: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non-small cell lung cancer (NSCLC), but previous work focused on patients with advanced-stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC. METHOD: Consecutive patients with suspected lung cancer who underwent curative-intent lung resection were enrolled prospectively in this study...
May 24, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28625653/most-t790m-mutations-are-present-on-the-same-egfr-allele-as-activating-mutations-in-patients-with-non-small-cell-lung-cancer
#8
Noriko Hidaka, Eiji Iwama, Naoki Kubo, Taishi Harada, Kohta Miyawaki, Kentaro Tanaka, Isamu Okamoto, Eishi Baba, Koichi Akashi, Hiroyuki Sasaki, Yoichi Nakanishi
OBJECTIVES: The T790M and C797S mutations of the epidermal growth factor receptor gene (EGFR) confer resistance to first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), respectively, in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR. C797S has been identified in cis or in trans with T790M in tumor specimens from patients who experienced treatment failure with first- and third-generation EGFR-TKIs. The allelic relation between T790M and activating mutations of EGFR has not been well characterized, however...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28619094/morphologic-and-molecular-study-of-lung-cancers-associated-with-idiopathic-pulmonary-fibrosis-and-other-pulmonary-fibroses
#9
Alice Guyard, Claire Danel, Nathalie Théou-Anton, Marie-Pierre Debray, Laure Gibault, Pierre Mordant, Yves Castier, Bruno Crestani, Gérard Zalcman, Hélène Blons, Aurélie Cazes
BACKGROUND: Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). METHODS: Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28615371/a-phase-1b-open-label-multicentre-study-of-azd4547-in-patients-with-advanced-squamous-cell-lung-cancers
#10
Paul K Paik, Ronglai Shen, Michael F Berger, David Ferry, Jean-Charles Soria, Alastair Mathewson, Claire Rooney, Neil R Smith, Marie Cullberg, Elaine Kilgour, Donal Landers, Paul Frewer, A Nigel Brooks, Fabrice André
Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in ~20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with anti-tumor activity in FGFR1 amplified SQCLC cell lines and patient-derived xenografts. <br /><br />Experimental Design: Based on these data, we performed a phase 1 study of AZD4547 in patients with previously treated stage IV FGFR1 amplified SQCLCs (NCT00979134)...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28608966/next-generation-sequencing-and-clinical-outcomes-of-patients-with-lung-adenocarcinoma-treated-with-stereotactic-body-radiotherapy
#11
Richard J Cassidy, Xinyan Zhang, Pretesh R Patel, Joseph W Shelton, Chase E Escott, Gabriel L Sica, Michael R Rossi, Charles E Hill, Conor E Steuer, Rathi N Pillai, Suresh S Ramalingam, Taofeek K Owonikoko, Madhusmita Behera, Seth D Force, Felix G Fernandez, Walter J Curran, Kristin A Higgins
BACKGROUND: Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population...
June 13, 2017: Cancer
https://www.readbyqxmd.com/read/28607809/rapid-response-of-brain-metastasis-to-crizotinib-in-a-patient-with-klc1-alk-fusion-and-met-gene-amplification-positive-non-small-cell-lung-cancer-a-case-report
#12
Peng Wang, Pei Xiao, Yingnan Ye, Pengpeng Liu, Lei Han, Li Dong, Chunhua She, Jinpu Yu
Non-small cell lung cancer (NSCLC) ranks as the leading cause of cancer-related death in the world. Brain metastasis (BM) is a common complication of NSCLC, with 25%-40% of patients developing BM during the course of the disease. A significant strategy of local disease control in the central nervous system is radiation therapy. With the development of precision medicine, the concept of treating lung cancer BM has gradually changed. In this case, we performed a surgical procedure to obtain enough tumor tissue for the detection of the target gene and other related experiments after the patient was informed...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28607059/human-genome-wide-repair-map-of-dna-damage-caused-by-the-cigarette-smoke-carcinogen-benzo-a-pyrene
#13
Wentao Li, Jinchuan Hu, Ogun Adebali, Sheera Adar, Yanyan Yang, Yi-Ying Chiou, Aziz Sancar
Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is the major cause of lung cancer. BaP forms covalent DNA adducts after metabolic activation and induces mutations. We have developed a method for capturing oligonucleotides carrying bulky base adducts, including UV-induced cyclobutane pyrimidine dimers (CPDs) and BaP diol epoxide-deoxyguanosine (BPDE-dG), which are removed from the genome by nucleotide excision repair. The isolated oligonucleotides are ligated to adaptors, and after damage-specific immunoprecipitation, the adaptor-ligated oligonucleotides are converted to dsDNA with an appropriate translesion DNA synthesis (TLS) polymerase, followed by PCR amplification and next-generation sequencing (NGS) to generate genome-wide repair maps...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28606923/detection-of-driver-and-resistance-mutations-in-leptomeningeal-metastases-of-nsclc-by-next-generation-sequencing-of-cerebrospinal-fluid-circulating-tumor-cells
#14
Ben-Yuan Jiang, Yang-Si Li, Wei-Bang Guo, Xu-Chao Zhang, Zhihong Chen, Jian Su, Wenzhao Zhong, Xue-Ning Yang, Jinji Yang, Yang W Shao, Biao Huang, Yan-Hui Liu, Qing Zhou, Hai-Yan Tu, Hua-Jun Chen, Zhen Wang, Chongrui Xu, Bin-Chao Wang, Shu-Yu Wu, Cun-Yi Gao, Xian Zhang, Yi-Long Wu
<p>Leptomeningeal metastases (LM) are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of LM.</p> <br />Experimental Design: <p>We compared the CellSearch Assay™, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected LM. Next-Generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTCs) of 19 patients...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28606918/evaluation-of-tumor-derived-exosomal-mirna-as-potential-diagnostic-biomarkers-for-early-stage-non-small-cell-lung-cancer-using-next-generation-sequencing
#15
Xiance Jin, Yanfan Chen, Hanbin Chen, Shaoran Fei, Didi Chen, Xiaona Cai, Linger Liu, Baochai Lin, Huafang Su, Lihao Zhao, Meng Su, Huanle Pan, Lanxiao Shen, Deyao Xie, Congying Xie
<br />To identify tumor-derived exosomal biomarkers that are able to discriminate between adenocarcinoma (AC) and squamous cell carcinoma (SCC) as a non-invasive method in the early diagnosis of non-small-cell lung cancer (NSCLC). <br /><br />Experimental Design: <br />Tumor-derived exosomes from the plasma of early stage NSCLC patients were isolated. Exosomal miRNA profiling of 46 stage I NSCLC patients and 42 healthy individuals was performed using miRNA-seq to identify and validate AC- and SCC-specific miRNAs...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28596492/detection-of-tumor-derived-dna-dispersed-in-the-airway-improves-the-diagnostic-accuracy-of-bronchoscopy-for-lung-cancer
#16
Taichiro Goto, Yosuke Hirotsu, Takahiro Nakagomi, Daichi Shikata, Yujiro Yokoyama, Kenji Amemiya, Toshiharu Tsutsui, Yumiko Kakizaki, Toshio Oyama, Hitoshi Mochizuki, Yoshihiro Miyashita, Masao Omata
The diagnostic accuracy of bronchoscopy for detecting lung cancer, especially peripheral lung cancer with lesions outside the endoscopically visible range, remains unsatisfactory. The aim of this study was to perform next-generation sequencing on bronchoscopic specimens to determine whether this improves the accuracy of bronchoscopy for diagnosing lung cancer and to identify factors influencing sensitivity. The bronchoscopic sensitivity for diagnosing lung cancer was initially evaluated in 191 patients who underwent lobectomy after bronchoscopy at our hospital...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586760/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#17
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586388/a-prospective-pilot-study-of-genome-wide-exome-and-transcriptome-profiling-in-patients-with-small-cell-lung-cancer-progressing-after-first-line-therapy
#18
Glen J Weiss, Sara A Byron, Jessica Aldrich, Ashish Sangal, Heather Barilla, Jeffrey A Kiefer, John D Carpten, David W Craig, Timothy G Whitsett
BACKGROUND: Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. METHODS: Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment...
2017: PloS One
https://www.readbyqxmd.com/read/28573640/expanding-the-search-for-significant-egfr-mutations-in-nsclc-outside-of-the-tyrosine-kinase-domain-with-next-generation-sequencing
#19
Matthew K Stein, Lindsay Morris, Jennifer L Sullivan, Moon Fenton, Ari VanderWalde, Lee S Schwartzberg, Mike G Martin
While conventional organization of EGFR mutations in non-small cell lung cancer (NSCLC) includes classic lesions sensitive to tyrosine kinase inhibitors (TKI) and variants localized to the tyrosine kinase domain (TKD) in exons 18-21, next-generation sequencing (NGS) raises the prospect of identifying clinically relevant variants in extra-TKD regulatory regions. NSCLC patients at our institution who received tumor profiling with NGS from 2013 to 2015 were identified. EGFR mutations were arranged based upon their distribution relative to the TKD...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28561651/precision-oncology-who-how-what-when-and-when-not
#20
Lee Schwartzberg, Edward S Kim, David Liu, Deborah Schrag
Precision oncology, defined as molecular profiling of tumors to identify targetable alterations, is rapidly developing and has entered the mainstream of clinical practice. Genomic testing involves many stakeholders working in a coordinated fashion to deliver high-quality tissue samples to high-quality laboratories, where appropriate next-generation sequencing (NGS) molecular analysis leads to actionable results. Clinicians should be familiar with the types of genomic variants reported by the laboratory and the technology used to determine the results, including limitations of current testing methodologies and reports...
2017: American Society of Clinical Oncology Educational Book
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