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Next generation sequencing AND lung cancer

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https://www.readbyqxmd.com/read/28723342/molecular-analysis-of-circulating-free-dna-from-lung-cancer-patients-in-routine-laboratory-practice-a-cross-platform-comparison-of-three-different-molecular-methods-for-mutation-detection
#1
Stephan Bartels, Sascha Persing, Britta Hasemeier, Elisa Schipper, Hans Kreipe, Ulrich Lehmann
Cell-free DNA (cfDNA), which is isolated from blood plasma, represents a noninvasive source for the detection of mutations conferring resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small-cell lung cancer patients. In advanced disease stages, performing regular biopsies is often not possible because of the general health condition of the patients. Furthermore, a biopsy of a single tumor lesion or metastasis may not reflect the heterogeneous genotype of the tumor and its metastases...
July 16, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#2
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#3
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28717660/a-novel-molecular-diagnostics-platform-for-somatic-and-germline-precision-oncology
#4
Rubén Cabanillas, Marta Diñeiro, David Castillo, Patricia C Pruneda, Cristina Penas, Guadalupe A Cifuentes, Álvaro de Vicente, Noelia S Durán, Rebeca Álvarez, Gonzalo R Ordóñez, Juan Cadiñanos
BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28706762/metastatic-breast-cancer-with-brca-mutation-discovered-by-next-generation-sequencing-responding-to-olaparib
#5
Wajeeha Rizvi, Phu Truong, Quoc Truong
Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) mutations are associated with hereditary breast and ovarian cancer syndromes (HBOC). However, certain individuals with breast cancer do not meet high-risk factors for hereditary breast cancer screening based on age, family history, and biology of malignancy. We present a patient with relapsed breast cancer who developed progressive disease with significant tumor burden causing a recurrent pleural effusion. Next-generation sequencing (NGS) done on a tumor biopsy was positive for the BRCA2 mutation...
June 11, 2017: Curēus
https://www.readbyqxmd.com/read/28693210/resistance-to-epithelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-a-patient-with-transformation-from-lung-adenocarcinoma-to-small-cell-lung-cancer-a-case-report
#6
Liying Fang, Jian He, Jingwen Xia, Liang Dong, Xiujuan Zhang, Yaqin Chai, Ying Li, Mengjie Niu, Tianxing Hang, Shengqing Li
First-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the treatment of non-small cell lung cancer (non-SCLC) with EGFR-sensitive mutations. However, acquired resistance to these drugs was inevitable. The transformation of lung adenocarcinoma to SCLC following treatment with EGFR-TKIs is a rare phenomenon that contributes to resistance to EGFR-TKIs. The present case concerns a 74-year-old man previously diagnosed with and treated for pneumonia; however, this was later pathologically confirmed as lung adenocarcinoma by transbronchial lung biopsy...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693166/quantitative-analysis-and-clonal-characterization-of-t-cell-receptor-%C3%AE-repertoires-in-patients-with-advanced-non-small-cell-lung-cancer-treated-with-cancer-vaccine
#7
Tu Mai, Atsushi Takano, Hiroyuki Suzuki, Takashi Hirose, Takahiro Mori, Koji Teramoto, Kazuma Kiyotani, Yusuke Nakamura, Yataro Daigo
With the development of cancer immunotherapy that may activate T cells, a practical and quantitative method to improve monitoring and/or prediction of immunological response of patients as a predictive biomarker is of importance. To examine possible biomarkers for a therapeutic cancer vaccine containing a mixture of three epitope peptides derived from cell division-associated 1, lymphocyte antigen 6 complex locus K and insulin-like growth factor-II mRNA-binding protein 3, T-cell receptor β (TCRβ) repertoires of blood samples from 24 patients with human leukocyte antigen-A*2402-positive non-small cell lung cancer were characterized prior to and following 8 weeks of the cancer vaccine treatment, by applying a next-generation sequencing method...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#8
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28683468/correlation-between-circulating-mutant-dna-and-metabolic-tumour-burden-in-advanced-non-small-cell-lung-cancer-patients
#9
Anne Winther-Larsen, Christina Demuth, Joan Fledelius, Anne Tranberg Madsen, Karin Hjorthaug, Peter Meldgaard, Boe Sandahl Sorensen
BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival. METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28662214/rbm10-promotes-transformation-associated-processes-in-small-cell-lung-cancer-and-is-directly-regulated-by-rbm5
#10
Julie J Loiselle, Justin G Roy, Leslie C Sutherland
Lung cancers are the leading cause of cancer-related deaths worldwide, with small cell lung cancer (SCLC) being the most aggressive type. At the time of diagnosis, SCLC has usually already metastasized, and an astonishing 95% of patients eventually succumb to the disease. This highlights the need for more effective SCLC screening and treatment options. Interestingly, the earliest and most frequent genetic alteration associated with lung cancers involves a lesion in the region to which the RNA binding protein RBM5 maps...
2017: PloS One
https://www.readbyqxmd.com/read/28655866/microrna-profiling-associated-with-non-small-cell-lung-cancer-next-generation-sequencing-detection-experimental-validation-and-prognostic-value
#11
Sandra Gallach, Eloisa Jantus-Lewintre, Silvia Calabuig-Fariñas, David Montaner, Sergio Alonso, Rafael Sirera, Ana Blasco, Marta Usó, Ricardo Guijarro, Miguel Martorell, Carlos Camps
BACKGROUND: The average five-year survival index for non-small cell lung cancer (NSCLC) patients is approximately 15%. Emerging evidence indicates that microRNAs constitute a new class of gene regulators in humans that may play an important role in tumorigenesis. Hence, there is growing interest in studying their role as possible new biomarkers whose expression is aberrant in cancer. Therefore, in this study we identified deregulated miRNAs by next generation sequencing (NGS) and analyzed their prognostic value...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28645111/intersecting-transcriptomic-profiling-technologies-and-long-non-coding-rna-function-in-lung-adenocarcinoma-discovery-mechanisms-and-therapeutic-applications
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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