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Next generation sequencing AND lung cancer

J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
Vijayalakshmi Padmanabhan, Heather B Steinmetz, Elizabeth J Rizzo, Amber J Erskine, Tamara L Fairbank, Francine B de Abreu, Gregory J Tsongalis, Laura J Tafe
CONTEXT: -At our medical center, cytopathologists perform rapid on-site evaluation for specimen adequacy of fine-needle aspiration and touch imprint of needle core biopsy lung cancer samples. Two years ago the molecular diagnostics laboratory at our institution changed to next-generation sequencing using the Ion Torrent PGM and the 50-gene AmpliSeq Cancer Hotspot Panel v2 for analyzing mutations in a 50-gene cancer hot spot panel. This was associated with in a dramatic fall in adequacy rate (68%)...
October 20, 2016: Archives of Pathology & Laboratory Medicine
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
Jonas Leichsenring, Anna-Lena Volckmar, Nikolaus Magios, Cristiano Manuel Morais de Oliveira, Roland Penzel, Regine Brandt, Martina Kirchner, Farastuk Bozorgmehr, Michael Thomas, Peter Schirmacher, Arne Warth, Volker Endris, Albrecht Stenzinger
Patients with NSCLC harboring activating mutations in the EGFR benefit from targeted therapies. A synonymous polymorphism (rs1050171, p.Q787Q) was shown to be associated with improved overall survival (OS) in colorectal cancer patients. As data in NSCLC are limited, we retrospectively analyzed associations of p.Q787Q with clinicopathological parameters including clinical response and outcome in patients with lung adenocarcinoma (ADC) who received tyrosine kinase inhibitor (TKI) therapy. Of 642 ADC patients whose tumors were profiled by next generation sequencing, 102 (15...
October 17, 2016: Genes, Chromosomes & Cancer
Yutong He, Xinyuan Zhang, Liqun Wang, Ziqiang Tian, Qingyi Liu, Jifang Yao, Yueping Liu, Chuanbao Li, Li Min, Baoen Shan
Non-small cell lung cancer (NSCLC) is a major public health problem worldwide and leads to a high mortality. NSCLC is always diagnosed in late stages because of its unapparent symptoms. However, cell-free DNA (cfDNA) may serve as a new potential biomarker to detect early stage of non‑small cell lung cancer. Here we recruited 10 non-small cell lung cancer patients to obtain fresh tumor tissue, peripheral blood lymphocytes (PBLs), and plasma. CfDNAs from 13 elderly people and 7 middle-age smokers were also extracted as controls...
October 12, 2016: International Journal of Oncology
Na Zhou, Cong Min Liu, He Lei Hou, Chuan Tao Zhang, Dong Liu, Guan Qun Wang, Ke Wei Liu, Jing Juan Zhu, Hong Ying Lv, Tian Jun Li, Xiaochun Zhang
Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma, and no effective chemotherapy special for metaplastic carcinoma exists until now. As spindle cell carcinomas of the breast are typically "Triple Negative", endocrine therapy and molecular therapy targeted to Her2 might not be favorable, resulting in poor prognosis. Apatinib is currently being tested in patients with breast or lung cancers. Here we report a successful case using Apatinib to treat spindle cell carcinoma of breast...
October 11, 2016: Oncotarget
Fumio Imamura, Junji Uchida, Yoji Kukita, Toru Kumagai, Kazumi Nishino, Takako Inoue, Madoka Kimura, Kikuya Kato
OBJECTIVES: Early evaluation of the effect of treatment is helpful in the management of cancer patients. Circulating biomarkers are an ideal tool for this if they are highly specific to tumors and respond rapidly to tumor volume changes. Circulating tumor DNA (ctDNA) is one such candidate. We conducted a prospective study to test the utility of EGFR ctDNA in early evaluation of EGFR-TKI effects. RESULTS: Twenty-one patients with EGFR-mutant lung cancer who were naïve to EGFR-TKI were enrolled...
September 30, 2016: Oncotarget
Patrick H Lizotte, Elena V Ivanova, Mark M Awad, Robert E Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina Almonte, Grit S Herter-Sprie, Abigail Santos, Nora B Feeney, Cloud P Paweletz, Meghana M Kulkarni, Adam J Bass, Anil K Rustgi, Guo-Cheng Yuan, Donald W Kufe, Pasi A Jänne, Peter S Hammerman, Lynette M Sholl, F Stephen Hodi, William G Richards, Raphael Bueno, Jessie M English, Mark A Bittinger, Kwok-Kin Wong
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC)...
September 8, 2016: JCI Insight
Shumei Kato, Vivek Subbiah, Erica Marchlik, Sheryl K Elkin, Jennifer L Carter, Razelle Kurzrock
PURPOSE: Aberrations in genetic sequences encoding the tyrosine kinase receptor RET lead to oncogenic signaling that is targetable with anti-RET multi-kinase inhibitors. Understanding the comprehensive genomic landscape of RET aberrations across multiple cancers may facilitate clinical trial development targeting RET. EXPERIMENTAL DESIGN: We interrogated the molecular portfolio of 4,871 patients with diverse malignancies for the presence of RET aberrations using Clinical Laboratory Improvement Amendments (CLIA) certified targeted next-generation sequencing (NGS) of 182 or 236 gene panels...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kazuya Takamochi, Hiroko Ohmiya, Masayoshi Itoh, Kaoru Mogushi, Tsuyoshi Saito, Kieko Hara, Keiko Mitani, Yasushi Kogo, Yasunari Yamanaka, Jun Kawai, Yoshihide Hayashizaki, Shiaki Oh, Kenji Suzuki, Hideya Kawaji
BACKGROUND: Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed...
September 29, 2016: BMC Cancer
Philip C Mack, Kimberly C Banks, Oliver A Zill, Stefanie A Mortimer, Darya I Chudova, Justin Odegaard, Christine E Lee, Rebecca J Nagy, Helmy Eltoukhy, Amirali Talasaz, Richard Lanman, David R Gandara
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Sander Bins, Geert A Cirkel, Christa G Gadellaa-van Hooijdonk, Fleur Weeber, Isaac J Nijman, Annette H Bruggink, Paul J van Diest, Stefan M Willems, Wouter B Veldhuis, Michel M van den Heuvel, Rob J de Knegt, Marco J Koudijs, Erik van Werkhoven, Ron H J Mathijssen, Edwin Cuppen, Stefan Sleijfer, Jan H M Schellens, Emile E Voest, Marlies H G Langenberg, Maja J A de Jonge, Neeltje Steeghs, Martijn P Lolkema
BACKGROUND: The discovery of novel biomarkers that predict treatment response in advanced cancer patients requires acquisition of high-quality tumor samples. As cancer evolves over time, tissue is ideally obtained before the start of each treatment. Preferably, samples are freshly frozen to allow analysis by next-generation DNA/RNA sequencing (NGS) but also for making other emerging systematic techniques such as proteomics and metabolomics possible. Here, we describe the first 469 image-guided biopsies collected in a large collaboration in The Netherlands (Center for Personalized Cancer Treatment) and show the utility of these specimens for NGS analysis...
September 23, 2016: Oncologist
Laura J Tafe, Kirsten J Pierce, Jason D Peterson, Francine de Abreu, Vincent A Memoli, Candice C Black, Jason R Pettus, Jonathan D Marotti, Edward J Gutmann, Xiaoying Liu, Keisuke Shirai, Konstantin H Dragnev, Christopher I Amos, Gregory J Tsongalis
Detection of somatic mutations in non-small cell lung cancers (NSCLCs), especially adenocarcinomas, is important for directing patient care when targeted therapy is available. Here, we present our experience with genotyping NSCLC using the Ion Torrent Personal Genome Machine (PGM) and the AmpliSeq Cancer Hotspot Panel v2. We tested 453 NSCLC samples from 407 individual patients using the 50 gene AmpliSeq Cancer Hotspot Panel v2 from May 2013 to July 2015. Using 10 ng of DNA, up to 11 samples were simultaneously sequenced on the Ion Torrent PGM (316 and 318 chips)...
September 2016: Neoplasia: An International Journal for Oncology Research
Nadezda P Velizheva, Markus P Rechsteiner, Christine E Wong, Qing Zhong, Matthias Rössle, Beata Bode, Holger Moch, Alex Soltermann, Peter J Wild, Verena Tischler
BACKGROUND: Molecular testing of lung adenocarcinomas (ADCs) is crucial for therapy stratification of patients. Because of the often limited diagnostic material, the authors aimed to explore the suitability of cytology smears for next-generation sequencing (NGS) and compared the results with concurrent histological specimens or cell blocks. METHODS: A total of 16 formalin-fixed paraffin-embedded (FFPE) ADCs with known genetic alterations were used as the first cohort for targeted DNA and RNA sequencing...
September 16, 2016: Cancer Cytopathology
Joanne Kotsopoulos, Victoria Sopik, Barry Rosen, Isabel Fan, John R McLaughlin, Harvey Risch, Ping Sun, Steven A Narod, Mohammad R Akbari
Recent studies suggest that mutations in the partner and localizer of BRCA2 (PALB2) gene may predispose to ovarian cancer. It is of importance to clarify the prevalence and penetrance of PALB2 mutations in an unselected population so that clinical recommendations for prevention can be implemented. We evaluated the prevalence of germline mutations in PALB2 among 1421 epithelial ovarian cancer patients and 4300 European controls from the National Heart, Lung, and Blood Institute's Exome Sequencing Project dataset...
September 8, 2016: Familial Cancer
Laetitia Borsu, Julie Intrieri, Linta Thampi, Helena Yu, Gregory Riely, Khedoudja Nafa, Raghu Chandramohan, Marc Ladanyi, Maria E Arcila
Although next-generation sequencing (NGS) is a robust technology for comprehensive assessment of EGFR mutant lung adenocarcinomas (LADs) with acquired resistance to tyrosine kinase inhibitors, it may not provide sufficiently rapid and sensitive detection of the EGFR T790M mutation, the most clinically relevant resistance biomarker. Here, we describe a digital PCR (dPCR) assay for rapid T790M detection on aliquots of NGS libraries prepared for comprehensive profiling, fully maximizing broad genomic analysis on limited samples...
September 12, 2016: Journal of Molecular Diagnostics: JMD
Pamela J Kaisaki, Anthony Cutts, Niko Popitsch, Carme Camps, Melissa M Pentony, Gareth Wilson, Suzanne Page, Kulvinder Kaur, Dimitris Vavoulis, Shirley Henderson, Avinash Gupta, Mark R Middleton, Ioannis Karydis, Denis C Talbot, Anna Schuh, Jenny C Taylor
Use of circulating tumour DNA (ctDNA) as a liquid biopsy has been proposed for potential identification and monitoring of solid tumours. We investigate a next-generation sequencing approach for mutation detection in ctDNA in two related studies using a targeted panel. The first study was retrospective, using blood samples taken from melanoma patients at diverse timepoints before or after treatment, aiming to evaluate correlation between mutations identified in biopsy and ctDNA, and to acquire a first impression of influencing factors...
2016: PloS One
Nicolas Pécuchet, Yves Rozenholc, Eleonora Zonta, Daniel Pietraz, Audrey Didelot, Pierre Combe, Laure Gibault, Jean-Baptiste Bachet, Valérie Taly, Elizabeth Fabre, Hélène Blons, Pierre Laurent-Puig
BACKGROUND: Detecting single-nucleotide variations and insertions/deletions in circulating tumor DNA is challenging because of their low allele frequency. The clinical use of circulating tumor DNA to characterize tumor genetic alterations requires new methods based on next-generation sequencing. METHODS: We developed a method based on quantification of error rate of each base position [position error rate (PER)]. To identify mutations, a binomial test was used to compare the minor-allele frequency to the measured PER at each base position...
September 13, 2016: Clinical Chemistry
Victoria Villaflor, Brian Won, Rebecca Nagy, Kimberly Banks, Richard B Lanman, AmirAli Talasaz, Ravi Salgia
INTRODUCTION: The potential of oncogene-driven targeted therapy is perhaps most fully realized in non-small cell lung cancer (NSCLC), given the number of genomic targets and approved matched therapies. However, invasive tissue biopsy at the time of each disease progression may not be possible and is associated with high morbidity and cost. Use of newly available "liquid biopsies" can circumvent these issues. RESULTS: 83% of subjects had at least one genomic alteration identified in plasma...
September 1, 2016: Oncotarget
Jeffrey C Thompson, Stephanie S Yee, Andrea B Troxel, Samantha L Savitch, Ryan Fan, David Balli, David B Lieberman, Jennifer D Morrissette, Tracey L Evans, Joshua Bauml, Charu Aggarwal, John A Kosteva, Evan Alley, Christine Ciunci, Roger B Cohen, Stephen Bagley, Susan Stonehouse-Lee, Victoria E Sherry, Elizabeth Gilbert, Corey Langer, Anil Vachani, Erica L Carpenter
PURPOSE: The expanding number of targeted therapeutics for non-small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS. EXPERIMENTAL DESIGN: 112 plasma samples obtained from a consecutive study of 102 prospectively enrolled patients with advanced NSCLC were subjected to ultra-deep sequencing of up to 70 genes and matched with tissue samples, when possible...
September 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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