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Driver mutation lung cancer

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https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#1
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#2
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28535939/gene-expression-profiling-of-large-cell-lung-cancer-links-transcriptional-phenotypes-to-the-new-histological-who2015-classification
#3
Anna Karlsson, Hans Brunnström, Patrick Micke, Srinivas Veerla, Johanna Mattsson, Linnea La Fleur, Johan Botling, Mats Jönsson, Christel Reuterswärd, Maria Planck, Johan Staaf
INTRODUCTION: Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes a small proportion of non-small cell lung cancer (NSCLC). The WHO2015 classification guidelines changed the definition of the debated histological subtype LC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine if these new guidelines translate also to the transcriptional landscape of lung cancer, and LC specifically. METHODS: Gene expression profiling was performed using Illumina V4 HT12 microarrays on 159 cases (comprising all histological subtypes including 10 WHO2015 LC and 14 LCNEC tumors), with complimentary mutational and IHC data...
May 20, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28532538/-aberrant-expression-of-rb-and-prb-780-prb-795-in-lung-adenocarcinoma-patients-with-egfr-mutations-and-their-clinical-significance
#4
Yunlong Dong, Minghui Liu, Yongwen Li, Ying Li, Chenlong Zhao, Yin Yuan, Hui Du, Zihe Zhang, Hongbing Zhang, Hongyu Liu, Jun Chen
BACKGROUND: Rb is an important tumor suppressor gene that regulates cell cycle progression. Rb dysfunction can lead to over proliferation of cells and lead to the occurrence of tumor. Loss or reduced Rb expression as well as over phosphorylation of Rb are important mechanisms of Rb dysfunction. The mutated epidermal growth factor receptor (EGFR) gene is an important driver gene in lung adenocarcinoma, and plays an important role in the development of lung cancer. The purpose of this study was to investigate the status of Rb in lung adenocarcinoma patients with EGFR mutations and define the clinicopathologic features...
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28529628/cross-platform-comparison-of-four-leading-technologies-for-detecting-egfr-mutations-in-circulating-tumor-dna-from-non-small-cell-lung-carcinoma-patient-plasma
#5
Ting Xu, Xiaozheng Kang, Xiaofang You, Liang Dai, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu
Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison...
2017: Theranostics
https://www.readbyqxmd.com/read/28507205/a-case-of-metastatic-atypical-neuroendocrine-tumor-with-alk-translocation-and-diffuse-brain-metastases
#6
Victoria E Wang, Lauren Young, Siraj Ali, Vincent A Miller, Anatoly Urisman, John Wolfe, Trever G Bivona, Bertil Damato, Shannon Fogh, Emily K Bergsland
A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies...
May 15, 2017: Oncologist
https://www.readbyqxmd.com/read/28502721/met-exon-14-skipping-mutations-in-lung-adenocarcinoma-clinicopathologic-implications-and-prognostic-values
#7
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-Bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
INTRODUCTION: Response to MET inhibitors in non-small cell lung cancer with MET exon 14 (METex14) skipping has fueled molecular screening efforts and search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping METHODS: Among 795 East-Asian patients who underwent surgery for non-small cell lung cancer, we screened 45 patients with quintuple-negative (EGFR-/KRAS-/ALK-/ROS1-/RET-) lung adenocarcinomas using RT-PCR, and found 17 patients (37...
May 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28490925/management-of-egfr-mutated-non-small-cell-lung-cancer-practical-implications-from-a-clinical-and-pathology-perspective
#8
REVIEW
M Cabanero, R Sangha, B S Sheffield, M Sukhai, M Pakkal, S Kamel-Reid, A Karsan, D Ionescu, R A Juergens, C Butts, M S Tsao
Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28487464/targeting-braf-mutant-non-small-cell-lung-cancer-from-molecular-profiling-to-rationally-designed-therapy
#9
Christina S Baik, Nathaniel J Myall, Heather A Wakelee
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths globally. However, the identification of oncogenic driver alterations involved in the initiation and maintenance of NSCLC, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocation, has led to the development of novel therapies that directly target mutant proteins and associated signaling pathways, resulting in improved clinical outcomes. As sequencing techniques have improved, the molecular heterogeneity of NSCLC has become apparent, leading to the identification of a number of potentially actionable oncogenic driver mutations...
May 9, 2017: Oncologist
https://www.readbyqxmd.com/read/28484014/selective-targeting-of-point-mutated-kras-through-artificial-micrornas
#10
Mario Acunzo, Giulia Romano, Giovanni Nigita, Dario Veneziano, Luigi Fattore, Alessandro Laganà, Nicola Zanesi, Paolo Fadda, Matteo Fassan, Lara Rizzotto, Raleigh Kladney, Vincenzo Coppola, Carlo M Croce
Mutated protein-coding genes drive the molecular pathogenesis of many diseases, including cancer. Specifically, mutated KRAS is a documented driver for malignant transformation, occurring early during the pathogenesis of cancers such as lung and pancreatic adenocarcinomas. Therapeutically, the indiscriminate targeting of wild-type and point-mutated transcripts represents an important limitation. Here, we leveraged on the design of miRNA-like artificial molecules (amiRNAs) to specifically target point-mutated genes, such as KRAS, without affecting their wild-type counterparts...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28479369/genomic-profiling-of-advanced-non-small-cell-lung-cancer-in-community-settings-gaps-and-opportunities
#11
Martin E Gutierrez, Kelly Choi, Richard B Lanman, Edward J Licitra, Stanley M Skrzypczak, Ruth Pe Benito, Tommy Wu, Srikesh Arunajadai, Sukhi Kaur, Harry Harper, Andrew L Pecora, Eric V Schultz, Stuart L Goldberg
BACKGROUND: National guidelines have advocated broad molecular profiling as a part of the standard diagnostic evaluation for advanced non-small cell lung cancer (NSCLC), with the goal of identifying driver mutations for which effective therapies or clinical trials are available. However, adherence to genomic testing guidelines could present challenges to community oncologists. PATIENTS AND METHODS: We performed a retrospective review of genomic testing patterns in patients with nonsquamous NSCLC treated by 89 oncologists at 15 sites throughout New Jersey and Maryland from January 2013 to December 2015...
April 13, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28472989/circulating-mutational-portrait-of-cancer-manifestation-of-aggressive-clonal-events-in-both-early-and-late-stages
#12
Meng Yang, Umit Topaloglu, W Jeffrey Petty, Matthew Pagni, Kristie L Foley, Stefan C Grant, Mac Robinson, Rhonda L Bitting, Alexandra Thomas, Angela T Alistar, Rodwige J Desnoyers, Michael Goodman, Carol Albright, Mercedes Porosnicu, Mihaela Vatca, Shadi A Qasem, Barry DeYoung, Ville Kytola, Matti Nykter, Kexin Chen, Edward A Levine, Edgar D Staren, Ralph B D'Agostino, Robin M Petro, William Blackstock, Bayard L Powell, Edward Abraham, Boris Pasche, Wei Zhang
BACKGROUND: Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. METHODS: We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins...
May 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28469388/significant-prognostic-features-and-patterns-of-somatic-tp53-mutations-in-human-cancers
#13
Wensheng Zhang, Andrea Edwards, Erik K Flemington, Kun Zhang
TP53 is the most frequently altered gene in human cancers. Numerous retrospective studies have related its mutation and abnormal p53 protein expression to poor patient survival. Nonetheless, the clinical significance of TP53 (p53) status has been a controversial issue. In this work, we aimed to characterize TP53 somatic mutations in tumor cells across multiple cancer types, primarily focusing on several less investigated features of the mutation spectra, and determine their prognostic implications. We performed an integrative study on the clinically annotated genomic data released by The Cancer Genome Atlas...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28453411/pooled-analysis-of-the-prognostic-and-predictive-effects-of-tp53-comutation-status-combined-with-kras-or-egfr-mutation-in-early-stage-resected-non-small-cell-lung-cancer-in-four-trials-of-adjuvant-chemotherapy
#14
Frances A Shepherd, Benjamin Lacas, Gwénaël Le Teuff, Pierre Hainaut, Pasi A Jänne, Jean-Pierre Pignon, Thierry Le Chevalier, Lesley Seymour, Jean-Yves Douillard, Stephen Graziano, Elizabeth Brambilla, Robert Pirker, Martin Filipits, Robert Kratzke, Jean-Charles Soria, Ming-Sound Tsao
Purpose Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non-small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories. Primary and secondary end points of pooled analysis were overall survival and disease-free survival...
April 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28450729/collateral-sensitivity-networks-reveal-evolutionary-instability-and-novel-treatment-strategies-in-alk-mutated-non-small-cell-lung-cancer
#15
Andrew Dhawan, Daniel Nichol, Fumi Kinose, Mohamed E Abazeed, Andriy Marusyk, Eric B Haura, Jacob G Scott
Drug resistance remains an elusive problem in cancer therapy, particularly for novel targeted therapies. Much work is focused upon the development of an arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops over time. Currently, after failure of first line ALK TKI therapy, another ALK TKI is administered, though collateral sensitivity is not considered. To address this, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK TKIs, and performed a collateral sensitivity analysis...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448556/a-highly-specific-and-sensitive-massive-parallel-sequencer-based-test-for-somatic-mutations-in-non-small-cell-lung-cancer
#16
Yoshiaki Inoue, Jun Shiihara, Hitoshi Miyazawa, Hiromitsu Ohta, Megumi Higo, Yoshiaki Nagai, Kunihiko Kobayashi, Yasuo Saijo, Masanori Tsuchida, Mitsuo Nakayama, Koichi Hagiwara
Molecular targeting therapy for non-small cell lung cancer (NSCLC) has clarified the importance of mutation testing when selecting treatment regimens. As a result, multiple-gene mutation tests are urgently needed. We developed a next-generation sequencer (NGS)-based, multi-gene test named the MINtS for investigating driver mutations in both cytological specimens and snap-frozen tissue samples. The MINtS was used to investigate the EGFR, KRAS, BRAF genes from DNA, and the ERBB2, and the ALK, ROS1, and RET fusion genes from RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#17
Mariam Jamal-Hanjani, Gareth A Wilson, Nicholas McGranahan, Nicolai J Birkbak, Thomas B K Watkins, Selvaraju Veeriah, Seema Shafi, Diana H Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D Forster, Tanya Ahmad, Crispin T Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M Quinn, Phil A Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O'Sullivan, Helen L Lowe, John A Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A Shaw, Javier Herrero, Zoltan Szallasi, Roland F Schwarz, Aengus Stewart, Sergio A Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy...
April 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28442019/-progress-of-c-met-signaling-pathway-and-tkis-in-non-small-cell-lung-cancer
#18
Xiaoqing Yu, Yanjun Xu, Yun Fan
c-MET is considered a promising oncogenic driver in non-small cell lung cancer (NSCLC) after the discovery of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). MET activation including gene mutation, amplification and protein overexpression, all of these are potential therapeutic targets and are associated with poor prognosis. Clinical evidence suggests a role for MET activation as both a primary oncogenic driver in subsets of lung cancer, and as a secondary driver of acquired resistance to EGFR-tyrosine kinase inhibitor (TKI)...
April 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28438075/concomitant-presence-of-egfr-and-alk-fusion-gene-mutation-in-adenocarcinoma-of-lung-a-case-report-and-review-of-the-literature
#19
Nishitha Thumallapally, Hana Yu, Mohammad Farhan, Uroosa Ibrahim, Maricel Odiami
Empirical evidence has long suggested that oncogenic driver mutations in non-small-cell lung cancer are mutually independent. However, recent studies reported in pertinent literature reveal that concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement can occur in a subset of patients with NSCLC. In order to shed further light on this issue, we report a case of adenocarcinoma of lung harboring both EGFR mutation in exon 21 (L861Q) and ALK rearrangement...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28435024/lkb1-deletion-in-murine-b-lymphocytes-promotes-cell-death-and-cancer
#20
George P Souroullas, Yuri Fedoriw, Louis M Staudt, Norman E Sharpless
LKB1 (aka STK11) is a potent tumor suppressor in solid tumors such as melanoma and lung adenocarcinoma, but inactivation in hematopoietic cells causes cell death, without signs of tumorigenesis. We noted somatic LKB1 deletion or mutation at low frequency in human B cell lymphoma. In order to determine if LKB1 inactivation is a passenger or driver event in lymphoid cancers, we examined the effects of conditional inactivation of Lkb1 in murine lymphocytes. Consistent with prior reports, Lkb1 deletion in either T or B cells resulted in massive, lineage-specific apoptosis...
April 20, 2017: Experimental Hematology
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