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Cancer Next Generation Sequencing

Vasiliki Panou, Meghana Gadiraju, Arthur Wolin, Caroline M Weipert, Emily Skarda, Aliya N Husain, Jyoti D Patel, Buerkley Rose, Shannon R Zhang, Madison Weatherly, Viswateja Nelakuditi, Amy Knight Johnson, Maria Helgeson, David Fischer, Arpita Desai, Nanna Sulai, Lauren Ritterhouse, Oluf D Røe, Kiran K Turaga, Dezheng Huo, Jeremy Segal, Sabah Kadri, Zejuan Li, Hedy L Kindler, Jane E Churpek
Purpose The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM). Methods We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM. Results Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%)...
August 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
E F Gaffney, P H Riegman, W E Grizzle, P H Watson
The decision to use 10% neutral buffered formalin fixed, paraffin embedded (FFPE) archival pathology material may be dictated by the cancer research question or analytical technique, or may be governed by national ethical, legal and social implications (ELSI), biobank, and sample availability and access policy. Biobanked samples of common tumors are likely to be available, but not all samples will be annotated with treatment and outcomes data and this may limit their application. Tumors that are rare or very small exist mostly in FFPE pathology archives...
August 16, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Duguang Li, Xiaowei Qian, Peng Xu, Xiaodong Wang, Zhennan Li, Jianjun Qian, Jie Yao
Drug resistance is a major problem in the treatment of pancreatic cancer (PC). Long noncoding (lnc)RNAs modulate a variety of cellular processes. This study was carried out to identify lncRNAs that are differentially expressed in drug-resistant PC by next-generation RNA sequencing. We identified 205 differentially expressed lncRNAs (DELs) and 847 differentially expressed mRNAs (DEMs) in a comparison of gemcitabine-resistant and -sensitive SW1990 human PC cells. The expression levels of 12 randomly selected lncRNAs were confirmed by quantitative real-time PCR...
August 16, 2018: DNA and Cell Biology
Ye Wang, Philip D Howes, Eunjung Kim, Christopher D Spicer, Michael R Thomas, Yiyang Lin, Spencer W Crowder, Isaac J Pence, Molly M Stevens
Advances in nanotechnology have provided new opportunities for the design of next-generation nucleic acid biosensors and diagnostics. Indeed, combining advances in functional nanoparticles, DNA nanotechnology, and nuclease-enzyme-based amplification can give rise to new assays with advantageous properties. In this work, we developed a microRNA (miRNA) assay using bright fluorescent quantum dots (QDs), simple DNA probes, and the enzyme duplex-specific nuclease. We employed an isothermal target-recycling mechanism, where a single miRNA target triggers the cleavage of many DNA signal probes...
August 16, 2018: ACS Applied Materials & Interfaces
Justin T Matulay, Ashish M Kamat
Bladder cancer is a heterogeneous disease that poses unique challenges to the treating clinician. It can be limited to a relatively indolent papillary tumor with low potential for progression beyond this stage to muscle-invasive disease prone to distant metastasis. The former is best treated as conservatively as possible, whereas the latter requires aggressive surgical intervention with adjuvant therapies in order to provide the best clinical outcomes. Risk stratification traditionally uses clinicopathologic features of the disease to provide prognostic information that assists in choosing the best therapy for each individual patient...
2018: F1000Research
Winnie S Liang, Jo-Anne Vergilio, Bodour Salhia, Helen J Huang, Yasuhiro Oki, Ignacio Garrido-Laguna, Haeseong Park, Jason R Westin, Funda Meric-Bernstam, David Fabrizio, Vincent A Miller, Philip J Stephens, Michelle A Fanale, Jeffrey S Ross, Filip Janku
BACKGROUND: The genomic landscape of Hodgkin lymphoma (HL) has been difficult to characterize due to the paucity of neoplastic cells and an abundant microenvironment. Such characterization is needed in order to improve treatment strategies. MATERIALS AND METHODS: We performed comprehensive genomic profiling (CGP) using targeted next-generation sequencing on archival formalin-fixed paraffin embedded tumor samples from 63 patients to analyze the landscape of HL. RESULTS: CGP was successful for 49/63 archival specimens (78%), and revealed aberrations impacting genes including B2M , TP53 , and XPO1 (E571)...
August 14, 2018: Oncologist
R R Jiang, Y J Wang, X D Teng, L Xiao, H Bu, F Ye
Objective: To compare the performance of Miseq and Ion Torrent PGM platforms and library construction method for next-generation sequencing (NGS) technology for formalin-fixed and paraffin-embedded (FFPE) samples. Methods: A total of 204 FFPE cancer samples including 100 non-small cell lung cancers at the First Affiliated Hospital of Zhejiang University, and 104 colorectal cancers at West China Hospital of Sichuan University were retrospectively selected from January 2013 to December 2016. By using the same samples, DNA was extracted, and the same amount of DNA was used for library construction with the same kit, and sequenced on Miseq and Ion Torrent PGM respectively, after passing the quality control...
August 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Siddhartha Devarakonda, Federico Rotolo, Ming-Sound Tsao, Irena Lanc, Elisabeth Brambilla, Ashiq Masood, Ken A Olaussen, Robert Fulton, Shingo Sakashita, Anne McLeer-Florin, Keyue Ding, Gwénaël Le Teuff, Frances A Shepherd, Jean-Pierre Pignon, Stephen L Graziano, Robert Kratzke, Jean-Charles Soria, Lesley Seymour, Ramaswamy Govindan, Stefan Michiels
Purpose The survival benefit with adjuvant chemotherapy for patients with resected stage II-III non-small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers in these patients have not yielded clinically useful tests. We report findings from the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing and long-term outcomes data from > 900 patients with early-stage NSCLC treated prospectively in adjuvant landmark clinical trials...
August 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Wai Yeow Lee, Maulana Bachtiar, Cheryl C S Choo, Caroline G Lee
PubMed was text mined to glean insights into the role of Hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) from the massive number of publications (9249) available to date. Reports from ∼70 countries identified >1300 human genes associated with either the Core, Surface or X gene in HBV-associated HCC. One hundred and forty-three of these host genes, which can potentially yield 1180 biomolecular interactions, each were reported in at least three different publications to be associated with the same HBV...
August 13, 2018: Biological Reviews of the Cambridge Philosophical Society
M Orditura, C M Della Corte, A Diana, V Ciaramella, E Franzese, V Famiglietti, I Panarese, R Franco, A Grimaldi, A Lombardi, M Caraglia, A Santoriello, E Procaccini, E Lieto, E Maiello, F De Vita, F Ciardiello, F Morgillo
Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment...
August 4, 2018: Breast: Official Journal of the European Society of Mastology
Nirali M Patel, Heejoon Jo, David A Eberhard, Xiaoying Yin, Michele C Hayward, Matthew K Stein, David Neil Hayes, Juneko E Grilley-Olson
Neoplastic cellularity contributes to the analytic sensitivity of most present technologies for mutation detection, such that they underperform when stroma and inflammatory cells dilute a cancer specimen's variant fraction. Thus, tumor purity assessment by light microscopy is used to determine sample adequacy before sequencing and to interpret the significance of negative results and mutant allele fraction afterwards. However, pathologist estimates of tumor purity are imprecise and have limited reproducibility...
August 10, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Xun Chen, Jason Kost, Dawei Li
Many viruses are capable of integrating in the human genome, particularly viruses involved in tumorigenesis. Viral integrations can be considered genetic markers for discovering virus-caused cancers and inferring cancer cell development. Next-generation sequencing (NGS) technologies have been widely used to screen for viral integrations in cancer genomes, and a number of bioinformatics tools have been developed to detect viral integrations using NGS data. However, there has been no systematic comparison of the methods or software...
August 8, 2018: Briefings in Bioinformatics
Samuel Rack, Rizwana Rahman, Louise Carter, Craig McKay, Robert Metcalf
Salivary gland cancer is a rare disease comprising multiple biologically diverse disease entities. Clinical trials have had relatively less impact on clinical practice in comparison with other cancer types. Here we describe clinical trials recruiting in salivary gland cancer and 'basket studies' incorporating molecular analysis using next generation sequencing (NGS) to stratify patients for molecularly targeted therapies. A systematic review of clinicaltrials. gov, PUBMED and ASCO, ESMO and AACR meeting abstracts was performed to identify clinical trials recruiting either salivary gland cancer cohorts or 'basket studies' which would be suitable for salivary gland cancer patients...
August 13, 2018: Clinical Otolaryngology
Dana E Rathkopf, Howard I Scher
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline...
September 2018: Expert Review of Anticancer Therapy
Matthias F Froelich, Sebastian Stintzing, Jörg Kumbrink, Thomas G P Grünewald, Ulrich Mansmann, Volker Heinemann, Thomas Kirchner, Andreas Jung
Skin toxicity (ST) is a frequent adverse effect (AE) in anti-epidermal growth factor receptor (EGFR)-targeted treatment of metastatic colorectal cancer (mCRC) resulting in decreased quality of life and problems in clinical management. We wanted to identify biomarkers predicting ST in this setting and focused on 70 DNA polymorphisms associated with acne, the (immunoglobulin fragment crystallizable region) Fcγ-receptor pathway, and systemic lupus erythematosus (SLE) applying next-generation-sequencing (NGS)...
July 13, 2018: Oncotarget
Ibrahim Fahoum, Relly Forer, Dina Volodarsky, Inna Vulih, Tova Bick, Shada Sarji, Zeev Bamberger, Ofer Ben-Izhak, Edmond Sabo, Ruth Hershberg, Dov Hershkovitz
OBJECTIVE: Circulating tumor DNA is a promising noninvasive tool for cancer monitoring. One of the challenges in applying this tool is the detection of low-frequency mutations. The detection limit of these mutations varies between different molecular methods. The aim of this study is to characterize the factors affecting the limit of detection for epidermal growth factor receptor p.T790M mutation in circulating tumor DNA of patients with lung adenocarcinoma. METHODS: DNA was extracted from plasma samples of 102 patients...
January 1, 2018: Technology in Cancer Research & Treatment
Nicklas Juel Pedersen, David Hebbelstrup Jensen, Giedrius Lelkaitis, Katalin Kiss, Birgitte Wittenborg Charabi, Henrik Ullum, Lena Specht, Ane Yde Schmidt, Finn Cilius Nielsen, Christian von Buchwald
BACKGROUND: MicroRNAs (miRNAs) hold promise as diagnostic cancer biomarkers. Here we aimed to define the miRNome in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM), and to identify and validate new diagnostic miRNAs and miRNA combinations in formalin-fixed paraffin-embedded (FFPE) tissue samples and plasma samples. METHODS: We performed next-generation miRNA sequencing in FFPE tissue samples of OSCC (n = 80) and NOM (n = 8). Our findings were validated by quantitative polymerase chain reaction (qPCR) analysis of OSCC (n = 195) and NOM (n = 103) FFPE tissue samples, and plasma samples from OSCC patients (n = 55) and healthy persons (n = 18)...
August 2018: Oral Oncology
Kerstin Zwirner, Franz J Hilke, German Demidov, Stephan Ossowski, Cihan Gani, Olaf Rieß, Daniel Zips, Stefan Welz, Christopher Schroeder
BACKGROUND AND PURPOSE: Radiochemotherapy is a standard treatment option for patients with head and neck cancer (HNSCC). During radiation, local toxicities are common and need to be differentiated from infections. As levels of circulating cell-free DNA (cfDNA) are known to be elevated during infections, cfDNA might complement clinical parameters. The aim of the study was to investigate the dynamics of cfDNA during radiochemotherapy. MATERIAL AND METHODS: In total, 78 blood samples of 20 patients with HNSCC were analysed in this prospective biomarker study...
August 7, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Angelika Terbuch, Juanita Lopez
Dramatic success in cancer immunotherapy has been achieved over the last decade with the introduction of checkpoint inhibitors, leading to response rates higher than with chemotherapy in certain cancer types. These responses are often restricted to cancers that have a high mutational burden and show pre-existing T-cell infiltrates. Despite extensive efforts, therapeutic vaccines have been mostly unsuccessful in the clinic. With the introduction of next generation sequencing, the identification of individual mutations is possible, enabling the production of personalized cancer vaccines...
August 9, 2018: Vaccines
You-Cai Zhu, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Zheng-Bo Song, Kai-Qi Du, Gang Chen, Tang-Feng Lv, Yong Song
In non-small cell lung cancer (NSCLC), driver gene alterations, such as EGFR, ALK, MET, and ROS1, are usually mutually exclusive. Few clinical cases with co-existing ROS1 fusion and de-novo MET amplification have been reported. In addition, the efficacy of crizotinib in Chinese patients with driver co-existing alterations is uncertain. A 65-year-old female was diagnosed with lung adenocarcinoma metastatic to the brain. She had sufficient tumor tissue for detection of the target gene; however, common driver gene mutations, such as EGFR-wild and ALK-negative, were not initially detected...
August 10, 2018: Cancer Biology & Therapy
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